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Inflammation

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Toes inflamed by chilblains Inflammation (Latin, īnflammō, "I ignite, set alight") is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants.[1] The classical signs of acute inflammation are pain, heat, redness, swelling, and loss of function. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process. Inflammation is not a synonym for infection, even though the two are often correlated (the former often being a result of the latter), and despite the fact that words ending in the suffix itis (which refers to inflammation) are sometimes informally described as referring to infection. (For example, the word urethritis means only "urethral inflammation", but, because most cases are caused by infection, even healthcare providers may tell a patient "it means you have an infection.") Although infection is caused by a microorganism, inflammation is one of the responses of the organism to the pathogen. Inflammation can even occur in the absence of infection (such as in atherosclerosis), although such types of inflammation are usually maladaptive. Inflammation is a stereotyped response, and therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity, which is specific for each pathogen.[2] Progressive destruction of the tissue would compromise the survival of the organism. However, chronic inflammation can also lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer (e.g., gallbladder carcinoma). It is for that reason that inflammation is normally closely regulated by the body. Inflammation can be classified as either acute or chronic. Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes (especially granulocytes) from the blood into the injured tissues. A cascade of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells within the injured tissue. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.

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1 Causes 2 Types o 2.1 Cardinal signs o 2.2 Process of acute inflammation 3 Exudative component o 3.1 Vascular changes o 3.2 Plasma cascade systems o 3.3 Plasma-derived mediators 4 Cellular component o 4.1 Leukocyte extravasation o 4.2 Cell-derived mediators 5 Morphologic patterns 6 Inflammatory disorders o 6.1 Atherosclerosis o 6.2 Allergies o 6.3 Myopathies o 6.4 Leukocyte defects o 6.5 Pharmacological o 6.6 Cancer o 6.7 Resolution of inflammation o 6.8 Connection to depression 7 Systemic effects o 7.1 Acute-phase proteins o 7.2 Leukocyte numbers o 7.3 Systemic inflammation and obesity o 7.4 Systemic inflammation and overeating 8 Outcomes 9 Examples 10 Exercise and inflammation o 10.1 Exercise-induced acute inflammation o 10.2 Post-inflammatory muscle growth and repair o 10.3 Chronic inflammation and muscle loss o 10.4 Exercise as a treatment for inflammation o 10.5 Signal-to-noise theory 11 Diet and chronic inflammation 12 See also 13 References 14 External links

Causes
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Burns Chemical irritants

fibrosis. reactive oxygen species. injured tissues neutrophils (primarily). mononuclear cells (monocytes. or autoimmune reactions Mononuclear cells (monocytes. necrosis Major cells involved Primary mediators Onset Duration Outcomes Cardinal signs The classic signs and symptoms of acute inflammation: English Latin Redness Rubor* Swelling Tumor* Heat Calor* . abscess formation. viral infection. macrophages. blunt or penetrating Immune reactions due to hypersensitivity Ionizing radiation Foreign bodies. persistent foreign bodies. lymphocytes.          Frostbite Toxins Infection by pathogens Physical injury. and eosinophils (response to helminth worms and parasites). hydrolytic enzymes Delayed Up to many months. eicosanoids Immediate Few days Resolution. macrophages) Vasoactive amines. growth factors. or years Tissue destruction. dirt and debris Stress Trauma Alcohol Types      Appendicitis Bursitis Colitis Cystitis Dermatitis       Phlebitis RSD/CRPS Rhinitis Tendonitis Tonsillitis Vasculitis Comparison between acute and chronic inflammation: Acute Chronic Causative agent Bacterial pathogens. plasma cells). including splinters. basophils (inflammatory response). chronic inflammation Persistent acute inflammation due to non-degradable pathogens. fibroblasts IFN-γ and other cytokines.

. be present.[6] Process of acute inflammation . The traditional names for signs of inflammation come from Latin:      Dolor (pain) Calor (heat) Rubor (redness) Tumor (swelling) Functio laesa (loss of function)[7] The first four (classical signs) were described by Celsus (ca. but no single sign must. swelling is caused by accumulation of fluid. Immobility (loss of function).g.Pain Loss of function Dolor* Functio laesa** [3] All the above signs may be observed in specific instances. whereas acute inflammation of internal organs may not result in the full set. acute inflammation of the lung (pneumonia) does not cause pain unless the inflammation involves the parietal pleura. [3] These are the original. usually appearing within a few minutes or hours and ceasing upon the removal of the injurious stimulus.[8] while loss of function was added later by Galen[9] even though the attribution is disputed and the origination of the fifth sign has also been ascribed to Thomas Sydenham[10] and Virchow. as a matter of course. Swelling and Heat.[6] These five signs appear when acute inflammation occurs on the body's surface. ** Infected ingrown toenail showing the characteristic redness and swelling associated with acute inflammation Acute inflammation is a short-term process. * [4] Functio laesa is an apocryphal notion. or "cardinal signs" of inflammation. pain is due to release of chemicals[specify] that stimulate nerve endings.[5][6] Redness and heat are due to increased blood flow at body core temperature to the inflamed site. 30 BC–38 AD). Loss of function has multiple causes. as it is not unique to inflammation and is a characteristic of many disease states. which does have pain-sensitive nerve endings. Pain happens only where the appropriate sensory nerve endings exist in the inflamed area—e. Redness.[5] It is characterized by five cardinal signs:[6] The acronym that may be used for this is "PRISH" for Pain.

In addition to cell-derived mediators. which recognize molecules that are broadly shared by pathogens but distinguishable from host molecules. Inflammatory mediators have short half lives and are quickly degraded in the tissue. . dolor).Micrograph showing acute inflammation of the prostate gland with the characteristic neutrophilic infiltrate.g. Kupffer cells and mastocytes. histiocytes. outside of the blood vessels (extravasation) into the tissue. e. The mediator molecules also alter the blood vessels to permit the migration of leukocytes. burn. This extravasated fluid is funneled by lymphatics to the regional lymph nodes. These cells present on their surfaces certain receptors named pattern recognition receptors (PRRs). these cells undergo activation (one of their PRRs recognize a PAMP) and release inflammatory mediators responsible for the clinical signs of inflammation. or other injuries. This movement is achieved via the chemically induced dilation and increased permeability of blood vessels. The increased collection of fluid into the tissue causes it to swell (edema). The neutrophils migrate along a chemotactic gradient created by the local cells to reach the site of injury. The process of acute inflammation is initiated by cells already present in all tissues. flushing bacteria along to start the recognition and attack phase of the adaptive immune system. Increased permeability of the blood vessels results in an exudation (leakage) of plasma proteins and fluid into the tissue (edema). which manifests itself as swelling (tumor). At the onset of an infection. mainly neutrophils. Some of the released mediators such as bradykinin increase the sensitivity to pain (hyperalgesia. collectively referred to as pathogen-associated molecular patterns (PAMPs). containing important proteins such as fibrin and immunoglobulins (antibodies). which results in a net loss of blood plasma. mainly resident macrophages. into inflamed tissue. Vasodilation and its resulting increased blood flow causes the redness (rubor) and increased heat (calor). several acellular biochemical cascade systems consisting of preformed plasma proteins act in parallel to initiate and propagate the inflammatory response. H&E stain. dendritic cells.[5] The acute inflammatory response requires constant stimulation to be sustained.[5] The loss of function (functio laesa) is probably the result of a neurological reflex in response to pain. These include the complement system activated by bacteria and the coagulation and fibrinolysis systems activated by necrosis.[5] Exudative component The exudative component involves the movement of plasma fluid. a burn or a trauma. Hence. acute inflammation ceases once the stimulus has been removed.

cause smooth muscle contraction. increase vascular permeability. C8. which marks the invader as a target for phagocytosis. to counterbalance clotting and generate several other inflammatory mediators. which forms a protective protein mesh over sites of injury. Vasodilation occurs first at the arteriole level. and agglutination. C7. C3a stimulates histamine release by mast cells. thereby producing vasodilation.a condition characterized by enlarged vessels packed with cells. Increased permeability of the vessels results in the movement of plasma into the tissues. progressing to the capillary level. a process critical to their recruitment into the tissues. Plasma cascade systems     The complement system. which are induced by the actions of various inflammatory mediators. it in turn is able to activate three plasma systems involved in inflammation: the kinin system. It is also able to act as a chemoattractant to direct cells via chemotaxis to the site of inflammation. fibrinolysis system. and produces the MAC. C3b is able to bind to bacterial cell walls and act as an opsonin. The kinin system generates proteins capable of sustaining vasodilation and other physical inflammatory effects. thereby producing vasodilation. increased permeability and increased blood flow.Vascular changes Acute inflammation is characterized by marked vascular changes. or exposed basement membranes via conformational change. and coagulation system. A complex of the complement proteins C5b. The fibrinolysis system. A protein that circulates inactively. The coagulation system or clotting cascade. creates a cascade of chemical reactions that promotes opsonization. platelets. with resultant stasis due to the increase in the concentration of the cells within blood . which acts in opposition to the coagulation system. Plasma-derived mediators * non-exhaustive list Name Bradykinin Produced by Kinin system C3 Complement system Complement system C5a Factor XII (Hageman Factor) Membrane Liver Complement Description A vasoactive protein that is able to induce vasodilation. Stasis allows leukocytes to marginate (move) along the endothelium. Stimulates histamine release by mast cells. Normal flowing blood prevents this. Cleaves to produce C3a and C3b. chemotaxis. and . and brings about a net increase in the amount of blood present. as the shearing force along the periphery of the vessels moves cells in the blood into the middle of the vessel. when activated. C6. and induce pain. until activated by collagen. causing the redness and heat of inflammation. including vasodilation. When activated.

Fibrinolysis Able to break down fibrin clots. system Cellular component The cellular component involves leukocytes. acute inflammation is mediated by granulocytes. and cellular debris. which normally reside in blood and must move into the inflamed tissue via extravasation to aid in inflammation. Thrombin Coagulation can also bind to cells via the PAR1 receptor to trigger several system other inflammatory responses. which is able to insert into bacterial cell walls and causes cell lysis with ensuing death. Others release enzymatic granules that damage pathogenic invaders. therefore mechanisms exist to recruit and direct leukocytes to the appropriate place. Some act as phagocytes. Leukocytes also release inflammatory mediators that develop and maintain the inflammatory response.attack complex Plasmin Thrombin multiple units of C9. whereas chronic inflammation is mediated by mononuclear cells such as monocytes and lymphocytes. Leukocyte extravasation Neutrophils migrate from blood vessels to the infected tissue via chemotaxis. In general. The process . such as production of chemokines and nitric oxide. which aggregates to form a blood clot. The combination and activation of this range of complement proteins forms the membrane attack complex. where they remove pathogens through phagocytosis and degranulation Main article: Leukocyte extravasation Various leukocytes are critically involved in the initiation and maintenance of inflammation. cleave complement protein C3. ingesting bacteria. viruses. system and activate Factor XII. Cleaves the soluble plasma protein fibrinogen to produce insoluble fibrin. These cells must be able to get to the site of injury from their usual location in the blood.

These weakly bound leukocytes are free to detach if not activated by chemokines produced in injured tissue. Movement of leukocytes within the tissue via chemotaxis: Leukocytes reaching the tissue interstitium bind to extracellular matrix proteins via expressed integrins and CD44 to prevent their loss from the site. histamine is Mast cells. Chemoattractants cause the leukocytes to move along a chemotactic gradient towards the source of inflammation. promote the immediate expression of P-selectin on endothelial cell surfaces. Antiviral.of leukocyte movement from the blood to the tissues through the blood vessels is known as extravasation. Granules can be classified as either specific or azurophilic Enzymes Granulocytes depending upon the contents. Type Source . and are able to break down a number of substances. some of which may be plasma-derived proteins that allow these enzymes to act as inflammatory mediators. NK cells macrophage-activating factor. 2. which further slow leukocytes down. It basophils. Leukocyte localisation and recruitment to the endothelium local to the site of inflammation – involving margination and adhesion to the endothelial cells: Recruitment of leukocytes is receptor-mediated. which functions similarly to P-selectin. 3. Cell-derived mediators * non-exhaustive list Name Lysosome granules Histamine IFN-γ Description These cells contain a large variety of enzymes that perform a number of functions. known as transmigration. and can be divided up into a number of broad steps: 1. Vasoactive released in response to a number of stimuli. via the process of diapedesis: Chemokine gradients stimulate the adhered leukocytes to move between endothelial cells and pass the basement membrane into the tissues. Cytokines also induce the expression of immunoglobulin ligands such as ICAM-1 and VCAM-1 on endothelial cells. immunoregulatory. Stored in preformed granules. This receptor binds weakly to carbohydrate ligands on leukocyte surfaces and causes them to "roll" along the endothelial surface as bonds are made and broken. and anti-tumour properties. Migration across the endothelium. such as histamine. This interferon was originally called Cytokine T-cells. Activation increases the affinity of bound integrin receptors for immunoglobulin ligands on the endothelial cell surface. amine causes arteriole dilation and increased venous platelets permeability. Cytokines from injured cells induce the expression of E-selectin on endothelial cells. The products of inflammation. firmly binding the leukocytes to the endothelium. and is especially important in the maintenance of chronic inflammation.

production of cytokines. During inflammation of the intestine (Pseudomembranous colitis). or pyogenic bacteria are involved. such as cancer cells. Macrophages. Mast cells Prostaglandins Eicosanoid fever. Large. endothelial gene regulation. and is able to B4 induce the formation of reactive oxygen species and the release of lysosome enzymes by these cells. recruitment. In neutrophils. leprosy. Leukotriene Eicosanoid Leukocytes it is also a potent chemoattractant. IL-8 Chemokine Primarily macrophages Morphologic patterns Specific patterns of acute and chronic inflammation are seen during particular situations that arise in the body. aids in leukocyte Nitric oxide Soluble gas endothelial cells. Primarily chemotaxis. such as when inflammation occurs on an epithelial surface. with a weak effect on monocytes and eosinophils. such as loss of appetite and increased heart rate. Infection by pyogenic bacteria such as staphylococci is characteristic of this kind of inflammation. Fibrinous inflammation: Inflammation resulting in a large increase in vascular permeability allows fibrin to pass through the blood vessels.[5] a fibrinous exudate is deposited. If an appropriate procoagulative stimulus is present. Able to mediate leukocyte adhesion and activation. TNF. Purulent inflammation: Inflammation resulting in large amount of pus. reduces platelet aggregation. Both affect a wide variety of cells to induce many similar inflammatory reactions: fever.Activation and chemoattraction of neutrophils. Responsible for the systemic effects 1 of inflammation. The deposit sometimes forms a pseudomembrane sheet. direct antimicrobial activity in high some neurons concentrations. sarcoidosis. leukocyte adherence. Potent vasodilator. and fluid. which include among others tuberculosis.    Granulomatous inflammation: Characterised by the formation of granulomas. pseudomembranous tubes can be formed. limiting their function. A group of lipids that can cause vasodilation. This is commonly seen in serous cavities. . relaxes smooth muscle. and pain. dead cells. where the conversion of fibrinous exudate into a scar can occur between serous membranes.alpha inhibits osteoblast differentiation. and syphilis. they are the result of a limited but diverse number of diseases. allowing them to bind to the endothelium and migrate across it. activation of TNF-α and ILCytokines macrophages fibroblasts. localised collections of pus enclosed by surrounding tissues are called abscesses. which consists of neutrophils.

the thrombotic complications of atherosclerosis. exposing lower layers. These new findings provide important links between risk factors and the mechanisms of atherogenesis. The immune system is often involved with inflammatory disorders.  Serous inflammation: Characterised by the copious effusion of non-viscous serous fluid. demonstrated in both allergic reactions and some myopathies. Clinical studies have . but may be derived from blood plasma. commonly produced by mesothelial cells of serous membranes. Skin blisters exemplify this pattern of inflammation. atherosclerosis. Non-immune diseases with etiological origins in inflammatory processes include cancer. ultimately. and ischaemic heart disease. The subsequent excavation in the epithelium is known as an ulcer. Examples of disorders associated with inflammation include:                Acne vulgaris Asthma Autoimmune diseases Celiac disease Chronic prostatitis Glomerulonephritis Hypersensitivities Inflammatory bowel diseases Pelvic inflammatory disease Reperfusion injury Rheumatoid arthritis Sarcoidosis Transplant rejection Vasculitis Interstitial cystitis Atherosclerosis Main article: Atherosclerosis Atherosclerosis.[5] A large variety of proteins are involved in inflammation. formerly considered a bland lipid storage disease. Inflammatory disorders Inflammatory abnormalities are a large group of disorders that underlie a vast variety of human diseases. actually involves an ongoing inflammatory response. with many immune system disorders resulting in abnormal inflammation. Ulcerative inflammation: Inflammation occurring near an epithelium can result in the necrotic loss of tissue from the surface. and any one of them is open to a genetic mutation which impairs or otherwise dysregulates the normal function and expression of that protein. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and.

or produce microbicides (chronic granulomatous disease). leading to signs of muscle inflammation. polymyositis. such as systemic sclerosis. digest bacteria (Chediak-Higashi syndrome). defects in leukocyte function often result in a decreased capacity for inflammatory defense with subsequent vulnerability to infection. releasing vasoactive chemicals such as histamine. They may occur in conjunction with other immune disorders. as indicated by levels of the inflammatory marker C-reactive protein. which is caused by a hypersensitive response by skin mast cells to allergens. certain treatments that reduce coronary risk also limit inflammation. Pharmacological Certain drugs or exogenic chemical compounds are known to affect inflammation.[12] and anti-inflammatory drugs work specifically by inhibiting normal inflammatory components.shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients. prospectively defines risk of atherosclerotic complications. In the case of lipid lowering with statins. These chemicals propagate an excessive inflammatory response characterised by blood vessel dilation. A common example is hay fever.[5] Dysfunctional leukocytes may be unable to correctly bind to blood vessels due to surface receptor mutations. Pre-sensitised mast cells respond by degranulating.[5] Myopathies Inflammatory myopathies are caused by the immune system inappropriately attacking components of muscle. These new insights into inflammation in atherosclerosis not only increase our understanding of this disease but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.[5] Leukocyte defects Due to the central role of leukocytes in the development and propagation of inflammation. and inclusion body myositis. Certain illicit drugs such as cocaine .[11] Allergies An allergic reaction. Vitamin A deficiency causes an increase in inflammatory responses. and include dermatomyositis. production of proinflammatory molecules. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes.[5] Severe inflammatory response may mature into a systemic response known as anaphylaxis. In addition. Other hypersensitivity reactions (type 2 and type 3) are mediated by antibody reactions and induce inflammation by attracting leukocytes that damage surrounding tissue. In addition. this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels. Moreover. and recruitment of leukocytes. thus adding to prognostic information provided by traditional risk factors. low-grade chronic inflammation. diseases affecting the bone marrow may result in abnormal or few leukocytes. cytokine release. is the result of an inappropriate immune response triggering inflammation. independently of myocardial damage. formally known as type 1 hypersensitivity.

[13][14] Cancer Inflammation orchestrates the microenvironment around tumours. Upregulation of anti-inflammatory molecules such as the Interleukin 1 receptor antagonist or the soluble tumor necrosis factor receptor (TNFR) Apoptosis of pro-inflammatory cells[25] Desensitization of receptors. Mechanisms that serve to terminate inflammation include:[5][19]             Short half-life of inflammatory mediators in vivo. due to the modular nature of many steroid hormone receptors.[15] Cancer cells use selectins. Such an approach may limit side effects that are unrelated to the tumor of interest.and ecstasy may exert some of their detrimental effects by activating transcription factors intimately involved with inflammation (e. many cells of the immune system contribute to cancer immunology. Resolution of inflammation occurs by different mechanisms in different tissues. Increased survival of cells in regions of inflammation due to their interaction with the extracellular matrix (ECM)[26][27] Downregulation of receptor activity by high concentrations of ligands Cleavage of chemokines by matrix metalloproteinases (MMPs) might lead to production of anti-inflammatory factors. which have important effects on cellular development. this interaction may offer ways to interfere with cancer progression.g. and may help preserve vital homeostatic functions and developmental processes in the organism. such as leukotrienes. Production and release of Transforming growth factor (TGF) beta from macrophages[20][21][22] Production and release of Interleukin 10 (IL-10)[23] Production of anti-inflammatory lipoxins[24] Downregulation of pro-inflammatory molecules. Resolution of inflammation The inflammatory response must be actively terminated when no longer needed to prevent unnecessary "bystander" damage to tissues. survival and migration. is very likely to affect carcinogenesis on the one hand. contributing to proliferation. suppressing cancer. on the other hand.[17] Molecular intersection between receptors of steroid hormones. such as NF-κB. through targeting of a specific protein domain in a specific cell type.[5] Failure to do so results in chronic inflammation. protectins or maresins.[16] On the other hand.[28] Production of resolvins. and cellular destruction.[18] This capacity of a mediator of inflammation to influence the effects of steroid hormones in cells. NF-κB). . may mediate some of the most critical effects of inflammatory stimuli on cancer cells. migration and metastasis. and transcription factors that play key roles in inflammation. chemokines and their receptors for invasion.

Acute-phase proteins Inflammation also induces high systemic levels of acute-phase proteins. of resolvins and protectins.[29] ” —Charles Serhan Connection to depression There is evidence for a link between inflammation and depression.[30] Inflammatory processes can be triggered by negative cognitions or their consequences. A pathogen can gain access to the bloodstream through lymphatic drainage into the circulatory system. these proteins prove beneficial. which cause a range of systemic effects including:[5] . Neutrophil recruitment thus ceases and programmed death by apoptosis is engaged. however in chronic inflammation they can contribute to amyloidosis. Vasodilation and organ dysfunction are serious problems associated with widespread infection that may lead to septic shock and death. and infection of a lymph node is known as lymphadenitis. An infection of the lymph vessels is known as lymphangitis. which critically shorten the period of neutrophil infiltration by initiating apoptosis. When it is due to infection. granulocytes promote the switch of arachidonic acid–derived prostaglandins and leukotrienes to lipoxins. which initiate the termination sequence. When lymph nodes cannot destroy all pathogens. As a consequence. apoptotic neutrophils undergo phagocytosis by macrophages. where it may spread to other parts of the body. After entering tissues.“ Acute inflammation normally resolves by mechanisms that have remained somewhat elusive. violence. or deprivation. These events coincide with the biosynthesis.[31][dubious – discuss] Systemic effects An infectious organism can escape the confines of the immediate tissue via the circulatory system or lymphatic system. the term sepsis is applied. from omega-3 polyunsaturated fatty acids. negative cognitions can cause inflammation that can. Thus. with the terms bacteremia being applied specifically for bacterial sepsis and viremia specifically to viral sepsis. and serum amyloid P. such as stress. the infection spreads further. Emerging evidence now suggests that an active.[5] These proteins include C-reactive protein. In acute inflammation. lead to depression. If an organism is not contained by the actions of acute inflammation it may gain access to the lymphatic system via nearby lymph vessels. coordinated program of resolution initiates in the first few hours after an inflammatory response begins. The anti-inflammatory program ends with the departure of macrophages through the lymphatics. serum amyloid A. leading to neutrophil clearance and release of antiinflammatory and reparative cytokines such as transforming growth factor-β1. When inflammation overwhelms the host. systemic inflammatory response syndrome is diagnosed. in turn.

TNF's primary .[38] A predominant factor in this correlation is due to the autoimmune response triggered by adiposity. the concept of systemic inflammation developed. and some cancers. some protozoa. especially immature cells. IL-6. hay fever. whereas diseases such as asthma. Although the processes involved are identical to tissue inflammation. where it results in a large increase in the amount of leukocytes in the blood. and parasite infestation result in an increase in eosinophils. systemic inflammation is not confined to a particular tissue but involves the endothelium and other organ systems.[5] Systemic inflammation and obesity With the discovery of interleukins (IL). whereby immune cells may mistake fatty deposits for intruders.      Fever Increased blood pressure Decreased sweating Malaise Loss of appetite Somnolence Leukocyte numbers Inflammation often affects the numbers of leukocytes present in the body:   Leukocytosis is often seen during inflammation induced by infection.[37] Waist circumference correlates significantly with systemic inflammatory response.[32] The obese commonly have many elevated markers of inflammation. including TNF-α and (IL-6).to threefold increase in the systemic concentrations of cytokines such as TNF-α. Then macrophages release inflammatory chemicals. creating eosinophilia. The body attacks fat similar to bacteria and fungi. Rickettsia infection. including viral infection. macrophages mobilize to clean up and embed into the adipose tissue. Leukocyte numbers usually increase to between 15 000 and 20 000 cells per microliter.[5] Leukopenia can be induced by certain infections and diseases. and CRP. but extreme cases can see it approach 100 000 cells per microliter. including:[33][34]         IL-6 (Interleukin-6)[35][36] IL-8 (Interleukin-8) IL-18 (Interleukin-18)[35][36] TNF-α (Tumor necrosis factor-alpha)[35][36] CRP (C-reactive protein)[35][36] Insulin[35][36] Blood glucose[35][36] Leptin[35][36] Low-grade chronic inflammation is characterized by a two. Chronic inflammation is widely observed in obesity. creating neutrophilia. tuberculosis.[5] Bacterial infection usually results in an increase of neutrophils. When expanded fat cells leak or break open.

[citation needed] Systemic inflammation and overeating Hyperglycemia induces IL-6 production from endothelial cells and macrophages. as an inflammatory marker. This link between adiposity and inflammation has been shown to produce 10-35% of IL-6 in a resting individual. she indicates that this is mediated via TNF-α. Mild elevation in CRP increase risk of heart attacks.[39] During clinical studies. Angptl2 then starts an inflammatory cascade causing blood vessels to remodel and attract macrophages.[41] In the obese mouse models. rather than secretes.[40] The association of systemic inflammation with insulin resistance and atherosclerosis is the subject of intense research.[citation needed] It is possible that. Higher than normal Angptl2 level in fat tissues develop inflammation as well as insulin and leptin resistance.. inflammatory-related molecule levels were reduced and increased levels of anti-inflammatory molecules were seen within four weeks after patients began a very low calorie diet. rather than Interleukin 6. it was commonly thought that the increase in IL-6 during exercise was a consequence of an immune response due to local damage in the working muscles and it was hypothesized that macrophages were responsible for this increase. Accordingly. It raises when there is inflammation throughout the body. There were also signs of dramatic increase in circulating insulin level. Bente Klarlund Pedersen wrote in 2013 that interstitial abdominal adiposity (also referred to as accumulated intra-abdominal fat) is a major and possibly primary factor in increasing systemic risk for multiple inflammatory diseases. Leptin resistance plays a role in the process where appetite overrules the message of satiety. leptin responds specifically to adipose-derived inflammatory cytokines. IL-6 during exercise. Pedersen concludes: "Until the beginning of this millennium.[43] Meals high in saturated fat. which she identified as a myokine in 2003. strokes. adipocyte lipolysis and formation of multinucleate giant cells. In addition. Stored fat secretes Leptin to signal satiety. White blood cells then assist by releasing more cytokines. We recently reported that insulin-resistant individuals demonstrated IL-6 resistance. Further work confirmed this finding at the protein level. high blood pressure. However. we suspect that muscle disuse may lead . as well as meals high in calories have been associated with increases in inflammatory markers.[46] Dr.role is to regulate the immune cells and induce inflammation. and this production increases with increasing adiposity.[42] The fat-derived protein called angiopoietin-like protein 2 (Angptl2) elevates in fat tissues. Angptl2 is an adipocyte-derived inflammatory mediator linking obesity to systemic insulin resistance. The finding that the nuclear transcription rate for IL-6 and the IL-6mRNA levels were rapidly and markedly increased after the onset of exercise suggested that a factor associated with contraction was responsible for the increase in IL-6 transcriptional rate within the nuclei from myocytes.. an early study demonstrated that IL-6 mRNA in monocytes did not increase as a result of exercise.. muscle weakness and fragility. However. C-reactive protein (CRP) is generated at a higher level in obese people. inflammation and macrophage-specific genes are upregulated in white adipose tissue (WAT). the liver clears. the response may become chronic if the overeating is chronic.[44][45] While the inflammatory responses are acute and arise in response to overeating.

which may be involved in the development of the TNF-α-induced insulin resistance in skeletal muscle. Importantly. as well as all-cause mortality independently of body mass index. colon cancer. also tumor initiation.. and it is likely that adipose tissue. it plays a direct role in the metabolic syndrome. is the main source of the circulating TNF-α. It is well known that both physical inactivity and abdominal adiposity are associated with persistent systemic low-grade inflammation. It has also been proposed that TNF-α causes insulin resistance indirectly in vivo by increasing the release of FFAs from adipose tissue. in CVDs. that is. The elevated circulating levels of IL-6 that accompany obesity and physical inactivity may represent a compensatory mechanism.‖ it will stimulate an inflammatory response. patients with diabetes have a high protein expression of TNF-α in skeletal muscle and increased TNF-α levels in plasma. Pedersen continues (in the same article): "Abdominal adiposity is associated with CVD. Accumulating data suggest that although TNF-α is not the pathogenetic factor. and breast cancer. Models of lipodystrophy suggest that if the subcutaneous fat becomes inflamed and adipocytes undergo apoptosis/necrosis. Thus. which produces TNF-α.. dementia.to IL-6 resistance. particularly in the etiology of atherosclerosis. activated immune cells also play major roles. it appears that the health consequences of abdominal adiposity and physical inactivity are very similar. One obvious explanation to the differential outcome of accumulating fat subcutaneously or as ectopic fat could be that when fat is stored in ―the wrong places. the fat storing capacity is impaired and fat will. also in people with a normal body weight. TNF-α has no effect on muscle fatty acid oxidation. evidence suggests that TNF-α plays a direct role in linking insulin resistance to vascular disease. type 2 diabetes. However. In addition. but increases fatty acid incorporation into diacylglycerol. In vitro studies demonstrate that TNF-α has direct inhibitory effects on insulin signaling. without an effect on EGP. Evidence exists that visceral fat is more inflamed than subcutaneous fat and constitutes an important source of systemic inflammation. as a consequence. In short.. TNF-α increases lipolysis in human and 3T3-L1 adipocytes. be deposited as ectopic fat. TNF-α infusion in healthy humans induces insulin resistance in skeletal muscle."[47] Outcomes . In addition."[47] Dr. This would be in line with the well-known facts that insulin resistance is accompanied by hyperinsulinemia and that chronic high circulating levels of leptin may reflect leptin resistance. Moreover. promotion. and progression is stimulated by systemic elevation of proinflammatory cytokines.

3. if the injurious agent persists then chronic inflammation will ensue. may lead to the formation of a chronic wound. This process. chemical production. Inflammatory measures such as vasodilation. cannot be regenerated completely by the body.  Acute appendicitis  Acute dermatitis . an opaque liquid containing dead white blood cells and bacteria with general debris from destroyed cells. Abscess Formation A cavity is formed containing pus. and damaged parenchymal cells regenerate. Resolution The complete restoration of the inflamed tissue back to a normal status. Chronic inflammation is characterised by the dominating presence of macrophages in the injured tissue. Here are the possible outcomes to inflammation:[5] 1. 2. Examples Inflammation is usually indicated by adding the suffix "itis". Chronic inflammation In acute inflammation. Fibrosis Large amounts of tissue destruction. forming a scar composed primarily of collagen. The scar will not contain any specialized structures. chronic inflammation is almost always accompanied by tissue destruction. as shown below. such as parenchymal cells. marked by inflammation lasting many days.Scars present on the skin. 4. However. More examples are available at list of types of inflammation. or damage in tissues unable to regenerate. hence functional impairment may occur. and leukocyte infiltration cease. evidence of fibrosis and healing of a wound The outcome in a particular circumstance will be determined by the tissue in which the injury has occurred and the injurious agent that is causing it. months or even years. Fibrous scarring occurs in these areas of damage. As a consequence. In situations where limited or short-lived inflammation has occurred this is usually the outcome. some conditions such as asthma and pneumonia do not follow this convention. These cells are powerful defensive agents of the body. but the toxins they release (including reactive oxygen species) are injurious to the organism's own tissues as well as invading agents.

which has been noted especially in marathon runners whose muscle fibers revealed remarkable damage to the muscle fibers after both training and marathon competition[citation needed]. Elevations in plasma enzymes. previously thought to cause muscle soreness. Participation in eccentric training and conditioning. in marathon runners and those who subscribe to the overload principle to enhance their muscles. This disruption of the muscle fibers triggers white blood cells to increase following the induced muscle soreness. Z-disks are the point of contact for the contractile proteins.[48] can result after induced eccentric and concentric muscle training. They provide structural support for the transmission of force when the muscle fibers are activated to shorten. were much higher with level running. The onset and timing of this gradient damage to the muscle parallels the degree of muscle soreness experienced by the runners. High tension in the contractile-elastic system of muscle results in structural damage to the muscle fiber and . and abnormal muscle histology and ultrastructure are concluded to be associated with the inflammatory response. Acute infective meningitis  Acute tonsillitis Exercise and inflammation Exercise-induced acute inflammation Acute inflammation of the muscle cells. including resistance training and activities that emphasize eccentric lengthening of the muscle including downhill running on a moderate to high incline can result in considerable soreness within 24 to 48 hours. as understood in exercise physiology. This delayed onset muscle soreness (DOMS) results from structural damage to the contractile filaments and z-disks. show moderate Z-disk streaming and major disruption of the thick and thin filaments in parallel groups of sarcomeres as a result of the force of eccentric actions or stretching of the tightened muscle fibers. However. leading to the inflammatory response observation from the induced muscle soreness. myoglobinemia. even though blood lactate levels.

NSAIDs) are able to blunt muscle growth. as described above. the increase in levels of IL-6 (Interleukin 6). as a response to muscle contractions. can reach up to one hundred times that of resting levels. That is.[51] The increase in cytokines (myokines) after resistance exercise coincides with the decrease in levels of myostatin. are a necessary precursor to muscle growth. Satellite cells are crucial for skeletal muscle adaption to exercise.[60] They contribute to hypertrophy by providing new myonuclei and repair damaged segments of mature myofibers for successful regeneration following injury.[61][62][63] high-level powerlifters can have up to 100% more satellite cells than untrained controls. intensity.[53] Muscles can synthesize cytokines in response to contractions. a myokine.[57][58][59] These acute increases in cytokines.or exercise-induced muscle damage.[64][65] A rapid and transient localization of the IL-6 receptor and increased IL-6 expression occurs in satellite cells following contractions.[57] IL-6 has been shown to mediate hypertrophic muscle growth both in vitro and in vivo. perimysium.[50][51] It has been further theorized that the acute localized inflammatory responses to muscular contraction during exercise. help initiate the process of muscle repair and growth by activating satellite cells within the inflamed muscle. especially at the 12-24 hour mark. Post-inflammatory muscle growth and repair There is a known relationship between inflammation and muscle growth. high doses of anti-inflammatory medicines (e.[54][55][56] such that the cytokines Interleukin-1 beta (IL-1β).plasmalemma and its epimysium. the IL-6 increase associated with training initiates about 4 hours after resistance training and remains elevated for up to 24 hours. TNF-α.g. contracting muscles release . and/or endomysium.[60] Unaccustomed exercise can increase IL-6 by up to sixfold at 5 hours post-exercise and threefold 8 days after exercise. in which large forces are distributed over a relatively small cross-sectional area of the muscle[citation needed]..[59] Developing research has demonstrated that many of the benefits of exercise are mediated through the role of skeletal muscle as an endocrine organ. kinins.[66] Also telling is the fact that NSAIDs can decrease satellite cell response to exercise. and IL-6 are expressed in skeletal muscle up to 5 days after exercise. The mysium damage disrupts calcium homeostasis in the injured fiber and fiber bundles.[50] thereby reducing exercise-induced protein synthesis. These substances then stimulate the free nerve endings in the muscle. and K+) accumulate outside the cells. a protein that inhibits muscle differentiation and growth. and other training factors. a process that appears accentuated by eccentric exercise.[53] In particular. the acute inflammatory response initiates the breakdown and removal of damaged muscle tissue.[49] For instance.[52] As a response to muscular contractions.[56] Depending on volume.[59] The cytokine response to resistance exercise and moderate-intensity running occur differently. with the latter causing a more prolonged response. resulting in necrosis that peaks about 48 hours after exercise. The products of the macrophage activity and intracellular contents (such as histamines.

[86] Marathon running may enhance IL-6 levels as much as 100 times over normal and increases total leuckocyte count and neturophil mobilization.[82] It may well be that low-intensity training can reduce resting pro-inflammatory markers (CRP.[86] Regarding the above. tissue repair. eccentric exercise may result in a delayed peak and a much slower decrease of plasma IL-6 during recovery. with the inhibition taking place preferentially in fasttwitch muscle fibers. IL-6). while moderate-intensity training has milder and less-established antiinflammatory benefits. mTOR loses its ability to be stimulated by muscle growth. Chronic inflammation has been implicated as part of the cause of the muscle loss that occurs with aging.[88] Recent work has shown that both upstream and downstream signalling pathways for IL-6 differ markedly between myocytes and macrophages. an extreme whole body inflammatory state. It appears that unlike IL-6 signalling in . As a matter of fact.[76] Exercise as a treatment for inflammation Regular physical activity is reported to decrease markers of inflammation.[49][67] Increased protein levels of myostatin have been described in patients with diseases characterized by chronic low-grade inflammation. This finding clearly demonstrates that muscle damage is not required to provoke an increase in plasma IL-6 during exercise. a crucial pathway for regulating skeletal muscle hypertrophy. For instance.[54] In animal models. including but not limited to those cited in the above description.[68] Increased levels of TNF-α can suppress the AKT/mTOR pathway. which in turn reduce the risk of developing various inflammatory diseases. while baseline measurements of circulating inflammatory markers do not seem to differ greatly between healthy trained and untrained adults. levels of the anti-inflammatory myokine IL-6 (Interleukin 6) remained elevated longer into the recovery period following an acute bout of exercise in patients with inflammatory diseases. when inflammation is created. which promote the growth of new tissue.[77][78][79] although the correlation is imperfect and seems to reveal differing results contingent upon training intensity. and various antiinflammatory functions. it has become evident that eccentric exercise is not associated with a larger increase in plasma IL-6 than exercise involving concentric ―nondamaging‖ muscle contractions.[80][83][84][85] There is a strong relationship between exhaustive exercise and chronic low-grade inflammation.[80][81] long-term training may help reduce chronic low-grade inflammation. it was first thought that the exercise-induced IL-6 response was related to muscle damage.[69] thereby increasing muscle catabolism.[73][74] In the case of sepsis. of the role of inflammation in adaptation to stress. IL-6 had previously been classified as a proinflammatory cytokine. relative to the recovery of healthy controls. The new view that muscle is an endocrine organ is transforming our understanding of exercise physiology and with it.[47] Chronic inflammation and muscle loss Both chronic and extreme inflammation are associated with disruptions of anabolic signals initiating muscle growth.[73][75] Sepsis is also able to prevent leucine from stimulating muscle protein synthesis. Therefore.[87] However.[70][71][72] Cytokines may antagonize the anabolic effects of Insulin-like growth factor 1 (IGF-1). the synthesis of both myofibrillar and sarcoplasmic proteins are inhibited.[82] On the other hand.multiple substances known as myokines.

low-grade inflammation. Foods from animals including meat and dairy. it has been theorized that a signal-to-noise model may best describe the relationship between inflammation and muscle growth. In general pro-inflammatory foods are highly processed or refined and fall into groups of "1. hydrogenated or damaged fats. in particular."[91] Examples of anti-inflammatory diets include the Mediterranean diet.[90] By keeping the "noise" of chronic inflammation to a minimum. Thus. pork and whole milk. the anti-inflammatory effects of IL-6 have been demonstrated by IL-6 stimulating the production of the classical anti-inflammatory cytokines IL-1ra and IL-10.[89] As such. Foods high in saturated. IL-6 was miscast as an inflammatory marker. Signal-to-noise theory Given that localized acute inflammation is a necessary component for muscle growth. though this concern rarely applies to the general population. Foods high on the glycemic scale. 3. Foods containing little or no fiber. and is antiinflammatory. (This is a long list) Flour containing gluten . and that chronic low-grade inflammation is associated with a disruption of anabolic signals initiating muscle growth. Note that cautions regarding over-exertion may apply in certain cases. as an inactive lifestyle is strongly associated with the development and progression of multiple inflammatory diseases.[89] Several studies show that markers of inflammation are reduced following longer-term behavioural changes involving both reduced energy intake and a regular program of increased physical activity. as discussed above. including the Ca2+/NFAT and glycogen/p38 MAPK pathways. Trans fat Sugar. other sweeteners and foods with added sugar or syrup. excepting cold water fish. 4. For example. 2. whereas IL-6 activation and signalling in muscle is totally independent of a preceding TNF-response or NFκB activation. These foods include:      Processed oils[92] Fatty meat and dairy including most beef. Diet and chronic inflammation See also: Anti-inflammatory foods The Western diet is known to contain many pro-inflammatory foods contributing to chronic.macrophages. when IL-6 is signalling in monocytes or macrophages. individuals pursuing exercise as a means to treat the causal factors underlying chronic inflammation are pursuing a course of action strongly supported by current research. and that. which is dependent upon activation of the NFκB signalling pathway. it creates a pro-inflammatory response. intramuscular IL-6 expression is regulated by a network of signalling cascades. foods which promote cytokine and eicosanoid production. the localized acute inflammatory response signals a stronger anabolic response than could be achieved with higher levels of chronic inflammation.

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