Biochemistry of Inflammation

Introduction to Inflammation
 Accompanied by the physical signs of heat, swelling, redness, and
pain, inflammation is a non-specific first line physiologic response
of the body to harmful stimuli such as:
 Pathogens
 Damaged cells,
 Chemicals or irradiation

 Inflammation is a defense
mechanism of the body

erythematosus (SLE)
involving activation, recruitment,
and action of cells of innate and
adaptive immunity to remove
Systemic lupus
injurious stimuli, followed by
restoration of the affected
tissues to their normal structural
and functional state by initiating
tissue repair, regeneration and
remodeling process.
 Introduction to Inflammation
 Inflammation involves an increase of the blood supply to the
affected region by means of vasodilation!!!

 The capillaries become more

permeable so that fluid, large
molecules, and white blood cells can
cross, leaving the blood and entering
the tissue

 White blood cells (particularly

neutrophils and monocytes) move by

Systemic lupus erythematosus (SLE)

chemotaxis to the injured site
 Chemotaxis is the directed
migration of cells in response to
concentration gradients of
extracellular signals.
 Introduction to Inflammation….
 Redness (rubor), heat (calor), swelling (tumor), and pain (dolor) are
associated with the inflammatory process
 Redness and heat are caused by the increased blood flow.

 Swelling is the result of the increased movement of fluid and white

blood cells into the area of inflammation

 Pain is caused by the release of chemical compounds and the

compression of nerves in the area of the inflammatory process

 During inflammation process , the chemical mediators of

inflammation are produced by activation of complement (a family of
blood proteins that are cleaved to form active fragments) or the blood
clotting cascade

 Mediators like histamine and kinins are released and increase

vascular permeability and stimulate the synthesis of eicosanoids that
act on the motility and metabolism of white blood cells and cause the
aggregation of platelets to arrest bleeding
 Introduction to Inflammation….
 Some of the prostaglandins which belong to a group of
eicosanoids act on thermoregulatory centers of the brain,
producing fever

 Cytokines are also released that stimulate the proliferation of cells

involved in the immune response

 Inflammation also contributes to the pathophysiology of many

chronic diseases like atherosclerosis
 Introduction to Inflammation….
 Inflammation contribute to other issues:
 Tissue injury
 Oxidative stress
 Remodeling of the extracellular matrix
 Angiogenesis, and
 Fibrosis ( fibrotic scarring) in diverse target tissues
 Inflammation leads to the pathogenesis of :
 Cancer
 Atherosclerosis
 Arthritis (Rheumatoid, Systemic lupus erythematosus (SLE))
 Crohn’s disease ( - a type of inflammatory bowel disease (IBD)
 Chronic obstructive pulmonary disease (COPD)
 Diabetes mellitus
 Asthma
 Heart disease
 Stroke
 multiple sclerosis and neurodegenerative diseases including
Alzheimer’s disease
 Introduction to Inflammation….
 Inflammation is one of the most central processes required in
defense of animal cells against certain injuries or microbial
infections

 Mechanism of inflammation represents a chain of organized,

dynamic responses including both cellular and vascular events
with specific humoral secretions

 These pathways involve changing physical location of white

blood cells (monocytes, basophils, eosinophils, and neutrophils),
plasma, and fluids at inflamed site

 A group of secreted mediators and other signaling molecules (e.g.,

histamine, prostaglandins, leukotrienes, oxygen- and nitrogen-
derived free radicals, and serotonin) are released by immune
defense cells in the mechanism which can contribute in the event of
inflammation.
 Types of Inflammation:
 Two types: Acute and Chronic
 Acute Inflammation
 Short duration
 Represents the early body reaction - followed by healing

 Acute: divided into: 1. Vascular 2. Cellular

1. Vascular:
 The responses which occur in microvasculature normally
appear in few minutes following tissue injury or microbial
infection in the presence of other inflammatory stimuli

 The occurrence of these processes is rapid and eventually will

lead to vasodilation and subsequently makes the vessels
become more permeable.

 This processes will result in entry of inflammatory mediators

and produces interstitial edema
 Introduction to Inflammation….
2. Cellular
 Cellular events encompass the successive capture, rolling,
and firming an adhesion to the microvascular endothelium

 These events in the mobilization pathway are arranged by cell

adhesion molecules (CAMs).

 CAMs include intracellular adhesion molecules (ICAM)-1,

ICAM-2, integrins, and selectin.
 Introduction to Inflammation….
 Chronic inflammation
 Longer duration- causative agent of acute inflammation persists
for a long time
 Chronic inflammation is caused due to a variety of diseases
including Neurodegenerative disorders; Cancer, and
Cardiovascular diseases
 The inflammation of chronic events are well known by :
 Mononuclear cell infiltration (e.g., monocyte and
lymphocytes),
 Fibroblasts proliferation,
 Collagen fibers, and connective tissue formation, which
ultimately result in granuloma
 With chronic inflammation, the tissue degeneration is normally
mediated by nitrogen species, proteases, and other reactive
oxygen species released from infiltrated inflammatory cells
 Genomic alterations in p53 (gene) may bring causes for many
chronic inflammatory diseases (e.g., inflammatory bowel
diseases and rheumatoid arthritis) and cancer
Introduction to Inflammation….
 Chemical Mediators of inflammation
1. Vasoactive Amines
 Histamine is released in a quantity of few pictograms from basophils
to maintain acute-phase response during inflammation events
 Serotonin is produced via decarboxylation of tryptophan, and it is
stored in the granule, in humans, it is present in platelets.

2. Peptide
 Bradykinin is a nano-peptide
 Similar to histamine and serotonin, it can increase the synthesis of
prostaglandins and produces pain locally

3. Eicosanoids
 Arachidonic acid, which represents the main component of
membrane phospholipids in all the cells, is one of the most important
substrates in the synthesis of biologically active mediators of the
inflammation called eicosanoids
 Leukotriene and 5-hydroxyeicosatetraenoic acid which produced
by 5-Lipoxygenase pathway
 Prostaglandins and thromboxanes are products of
Cyclooxygenases and 12- lipoxygenase (12-hydroxyeicosatetraenoic
 Chemical Mediators of Inflammation…
 Chemical mediators are responsible for vascular and cellular events
 Knowledge of these mediators – basis of anti-inflammatory drugs
 They are two types:
 Cell derived – produced locally by cells at the site of inflammation
 Plasma derived – mainly from liver
 Some mediators are derived from Necrotic cells

1. Cell-derived mediators
 Sequestered in intracellular granules
 Rapidly secreted upon cellular activation
 Example: Histamine in mast cells
 Synthesized from beginning in response to a stimulus,
 Example: Prostaglandins and cytokines
 Cell derived mediators can be:
 Vasoactive amines
 Arachidonic acid metabolites
 Lysosomal component
 Platelet activating factors (PAF)
 Cytokines
 Reactive oxygen species (ROS) and nitrogen oxide (NO)
 Neuropeptides
Chemical Mediators of Inflammation and their sources
 Chemical Mediators of Inflammation…
Vasoactive Amines
 Stored as preformed molecules in mast cells or early inflammatory cells
 Histamine
 Many cell types, particularly mast cells adjacent to vessels,
circulating basophils and platelets
 Histamine mediates wide range of cellular responses:-
 It is secreted by mast cells as a result of allergic reactions
or trauma
 It is also a powerful vasodilator
 It is involved in gastric acid
secretion
 It can possibly involve in
neurotransmission in parts
of the brain
 Formed by decarboxylation of
histidine by histidine
decarboxylase
 Inactivated by histaminase
 Chemical Mediators of Inflammation…
Vasoactive Amines…..
 Serotonin
 It can be also called 5-
hydroxytryptamine

 It has similar effects

with that of histamine
but less potent

 Released from platelet

dense body granules
during platelet
aggregation
 Chemical Mediators of Inflammation…
Peptides
 Kinins
 Kinins are potent peptide hormones formed de novo in body fluids
and tissues during inflammation

 They are derived from α-2 globulins (high and low molecular weight
kininogens) through proteolytic cleavage by a variety of enzymes
(the most important of which are plasma and tissue kallikreins)

 Three distinct kinins have been identified in humans:

 Bradykinin (Arg - Pro - Pro - Gly - Phe - Ser - Pro - Phe – Arg),
 Kallidin (lysbradykinin) (H-Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-
Phe-Arg-OH) and
 Met-lys-bradykinin(H-Met-Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-
Phe-Arg-OH)
 All of the kinins possess the same basic pharmacologic properties
(with few differences) including the induction of:
 Smooth muscle contractility,
 Vasodilation, and Increased capillary blood flow
 Chemical Mediators of Inflammation…
Eicosanoids
 Arachidonic acid Metabolites
 Involved in many biologic processes (including inflammation and
hemostasis)
 Short-range hormones that act locally at the site of generation
and then decay spontaneously or are enzymatically destroyed
 Derived from: Leukocytes, mast cells, endothelial cells, and
platelets, they are also derived from dietary linoleic acid
 Component of cell membrane phospholipids
 They are released from membrane phospholipids via cellular
phospholipases which are activated by mechanical, chemical, or
physical stimuli, or by inflammatory mediators such as
Complement component 5a (C5a)
 Undergo metabolism via either of this two major enzymatic
pathways
 Cyclooxygenase : prostaglandins and thromboxanes
 Lipoxygenase : leukotrienes and lipoxins
 Chemical Mediators of Inflammation…
 Arachidonic acid Metabolites….
 Cyclooxygenase Pathway
 Cyclooxygenase is an enzyme involved in the synthesis of
prostainoids including potent pro-inflammatory
prostaglandins and metabolism of arachidonic acid
 It exists in at least two isoforms: cyclooxygenase-1 and -2
(COX-1 and COX-2)
 Cyclooxygenase -1 is produced constitutively in most of the
mammal cell types and platelets
 It is also secreted in vascular endothelium, stomach,
forebrain, uterine epithelium, and kidney.
 It is stimulated at the site of inflammation
 Arachidonic acid metabolizes by this enzyme to the following
derivatives:
 Prostaglandins (PGD2, PGE2 and PGF2α)
 Thromboxane A= (TXA2)
 Prostacyclin (PGI2)
 Chemical Mediators of Inflammation…
 Arachidonic acid Metabolites….
 Cyclooxygenase Pathway….
 Major anti-inflammatory drugs which inhibit the activity of the
enzyme COX are Non-steroidal anti-inflammatory drugs
(NSAIDs)
 Example: Ibuprofen, diclofenac, indomethacin, high-
dose aspirin
 Lipoxygenase pathway
 Lipoxygenase is a predominant enzyme in neutrophils
 Acts on activated arachidonic acid to form Leukotrienes
(LT) and Lipoxins (LX)
Metabolism of Arachidonic acid
Examples of prostaglandin
structures.
[Note: Prostaglandins are named
as follows: PG plus a third letter
(for example, A, D, E, or F), which
designates the type and
arrangement of functional groups
in the molecule.
The subscript number indicates the
number of double bonds in the
mole cule. PGI2 is known as
prostacyclin. Thromboxanes are
designated by TX and leukotrienes
by LT.]
 Chemical Mediators of Inflammation…
Pathways for the metabolism of arachidonic acid

HETE = Hydroxy-eicosa-tetraenoic acid

 Function of Prostaglandins
 In the alimentary canal, prostaglandin-h and prostaglandin E2 inhibit secretion of gastric
acid, employ an uninterrupted vasodilator effect on the blood arteries and veins of the
gastric mucosa, and induce the viscous mucus creation which represents a protective
barrier .
 In the kidney, vasodilator prostaglandins (prostaglandin-h, prostaglandin E2, and
prostaglandin D2) account for a significant portion in dilating of renal vascular beds,
improving organ perfusion, regulating of renal blood flow, and shrinking of vascular
resistance .
 Prostaglandins (prostaglandin E2 and prostaglandin b) are substantially encompassed in
conserving the inflammatory process by increasing the vascular permeability and
strengthening the outcome of other inflammatory mediators such as kinin, serotonin, and
histamine and thus contributing to the redness, increased blood flow, and plasma
exudation in the area of acute inflammation which leads to edema .
 Prostaglandin E2 acts on neurons in the thermoregulatory network of the hypothalamus,
causing an increase in body temperature.
 Elevated levels of multiple prostaglandins including prostaglandin E2 and prostaglandin b
have been reported in synovial fluids from patients with rheumatoid arthritis and
osteoarthritis.
 Prostaglandins also play an important role in the pathogenesis of several types of cancers
such as breast, liver, and lung with overexpression of cyclooxygenase-2 and
overproduction of prostaglandin.
 Chemical Mediators of Inflammation…
 Leukotrienes
 Leukotrienes are generated by most cell types that participate in
inflammatory reactions including mast cells, basophils,
eosinophils, neutrophils, and monocytes

 As chemical mediators of inflammation, they have biologic

activity similar to that of histamine

 Leukotriene may involve in blocking the activity of G- protein

coupled receptor

 Leukotrienes are derived from arachidonic acid, which is made

available from cell membrane phospholipids by the action of:
 Phospholipase A, or
 By the sequential action of phospholipase C and
diacylglycerol lipase
 Chemical Mediators of Inflammation…

Release of arachidonic acid from membrane lipids. The binding

of a stimulus to its receptor activates pathway 1 or 2
 Chemical Mediators of Inflammation…
 Platelet Activating Factor (PAF)
 Phospholipid (membrane) - derived mediator with a broad
spectrum of inflammatory effects

 PAF may be produced by membranes of neutrophils, monocytes,

basophils, endothelial cells, and platelets and others (which
participate in the inflammatory response) by the action of
phospholipase A2

 The biologic Role : Platelet activation, activation of neutrophils,

and smooth muscle contraction.

 PAF stimulates the accumulation of eosinophils to endothelial

surfaces which can potentiate the inflammatory reaction.

 PAF stimulates eosinophils to release basic proteins, leading to

epithelial cell damage, and causes an increased expression of
low-affinity IgE receptors on eosinophils and monocytes
 Chemical Mediators of Inflammation…
 Tumor Necrosis Factor
 Produced by activated macrophages, as well as mast cells,
endothelial cells, and some other cell types

 Stimulated by microbial products, such as bacterial endotoxin,

immune complexes, and products of T lymphocytes

 Principal role in inflammation – endothelial activation

 Expression of adhesion molecules on endothelial cells -
increased leukocyte binding and recruitment,
 Enhance the production of additional cytokines (notably
chemokines) and eicosanoids

 TNF – increases thrombogenicity of endothelium and causes

aggregation and activation of neutrophils
 Chemical Mediators of Inflammation…
 Pro- inflammatory Cytokines (Chemokines)
 Polypeptide substances produced by activated lymphocytes
(lymphokines) and activated monocytes (monokines)

 Cytokines have important effects in the activity of many cells

particular they are important in regulating the immune system

 Major cytokines in acute inflammation induce the secretion of :

 Interleukin (IL)-1β, IL-8, IL-6, and IL-12
 Tumor necrosis factor alpha (TNF-α)

 Chronic inflammation:
 Interferon -γ (IFN-γ) and IL-12
 Based on the infection route, particularly, inflammatory response can be successful to get
rid of the causes of the disease. In such case, this response is acute (short-term) and limited
to the area where tissue damage occurs . This situation may lead to an increase in
macrophage-derived cytokine density in the plasma (Cytokine storm!!!!). These cytokines
affect other organs, especially the brain and liver, resulting in a systemic immune response
called the acute-phase response.
 Chemical Mediators of Inflammation…
Formation of Free Radicals During Phagocytosis and
Inflammation
 In response to infectious agents and other stimuli, phagocytic cells
of the immune system (neutrophils, eosinophils, and
monocytes/macrophages) exhibit a rapid consumption of O2 , the
condition which is called the respiratory burst

 Respiratory burst (also called oxidative burst) is the rapid

release of reactive oxygen species (superoxide anion and hydrogen
peroxide) from different types of cells.

 It is characterized by the generation of numerous oxidizing

molecules (free radicals) by two pathways:
 The superoxide pathway, leading to the generation of
reactive oxygen species (ROS), and

 The nitric oxide pathway, which leads to generate reactive

nitrogen oxygen species (RNOS)
Formation of free radicals during phagocytosis and inflammation..
 Therefor, the respiratory burst is a major source of:
 Reactive oxygen species (ROS), Superoxide radical (O 2-),
 Hydrogen peroxide (H2O2),
 The hydroxyl radical (OH-),
 Hypochlorous acid (HOCl), and
 Reactive Ntrogen oxygen species (RNOS ), Nitric oxide
(NO) – Free radicals

 The generation of free radicals is part of the human antimicrobial

defense system and is intended to destroy invading
microorganisms, tumor cells, and other cells targeted for
removal.
 In a number of disease states, free radical release by neutrophils
or macrophages during an inflammation contributes to injury in
the surrounding tissues!!!!!!
 During stroke or myocardial infarction, phagocytic cells that
move into the ischemic area to remove dead cells may
increase the area and extent of damage
 Chemical Mediators of Inflammation…
Formation of free radicals during phagocytosis and inflammation..
 The release of free radicals by neutrophils during inflammation
and immune complex formation may explain some of the features
of chronic inflammation in patients with rheumatoid arthritis

 As a result of free radical release, the immunoglobulin G (IgG)

proteins present in the synovial fluid are partially oxidized, which
improves their binding with the rheumatoid factor antibody and
this binding, in turn, stimulates the neutrophils to release more
free radicals
 Chemical Mediators of Inflammation…
 NADPH Oxidase
 It is an enzyme family widely expressed in many types of cells
including macrophage, phagocytes

 It produces superoxide, which spontaneously recombines with

other molecules to produce reactive free radicals

 During respiratory burst NADPH oxidase is activated and

catalyzes the transfer of an electron from NADPH to O2 to form
superoxide radical (O2·- )

 Superoxide is released into the intramembranous space of the

phagolysosome, where it is generally converted to hydrogen
peroxide and other ROS that are effective against bacteria and
fungal pathogens
 Hydrogen peroxide is formed by superoxide dismutase, which
may come from the phagocytic cell or the invading
microorganism
Formation of
Superoxide
radical,
Hydrogen
peroxide and
other radicals
 Chemical Mediators of inflammation…
 Myeloperoxidase (MPO) and HOCl
 The formation of hypochlorous acid from H2O2 is catalyzed by
myeloperoxidase, a heme-containing enzyme that is present only in
phagocytic cells of the immune system (predominantly neutrophils)
Myeloperoxidase Dissociation
H2O2 + Cl- + H+  HOCl + H2O -OCl + H+ + H2O
 Myeloperoxidase contains two Fe heme-like centers, which give it the
green color seen in pus
 Hypochlorous acid is a powerful toxin that destroys bacteria within
seconds through halogenation and oxidation reactions
 It oxidizes many Fe and S-containing groups (e.g., sulfhydryl groups,
iron-sulfur centers, ferredoxin, heme-proteins, methionine), oxidatively
decarboxylates and deaminates proteins, and cleaves peptide bonds

 Effects: Aerobic bacteria under attack rapidly lose membrane

transport, possibly because of damage to ATP synthase or electron
transport chain components (which reside in the plasma membrane
of bacteria)
Production of reactive oxygen species during the phagocytic respiratory burst by activated
neutrophils:
(1) Activation of NADPH oxidase on
the outer side of the plasma
membrane initiates the respiratory
burst with the generation of
superoxide. During phagocytosis, the
plasma membrane invaginates, so
superoxide is released into the
vacuole space.
(2) Superoxide (either spontaneously
or enzymatically via superoxide
dismutase [SOD]) generates H2O2.
(3) Granules containing
myeloperoxidase are secreted into the
phagosome, where myeloperoxidase
generates hypochlorous acid (HOCl)
and other halides.
(4) H2O2 can also generate the hydroxyl radical from the Fenton reaction.
(5) Inducible nitric oxide synthase may be activated and generate NO.
(6) Nitric oxide combines with superoxide to form peroxynitrite, which may generate additional
RNOS. The result is an attack on the membranes and other components of phagocytosed cells, and
eventual lysis. The whole process is referred to as the respiratory burst because it lasts only 30 to
60 minutes and consumes O2.
 Chemical Mediators of Inflammation…
 Reactive Oxygen Species (Superoxide radicals, O2·- )
 Synthesized via the NADPH oxidase – from neutrophils and
macrophages by microbes, immune complexes, cytokines, and a
variety of other inflammatory stimuli
 Within lysosomes - destroy phagocytosed microbes and necrotic
cells
 low levels:
 Increase chemokine, cytokine, and adhesion molecule
expression
 Amplifying the cascade of inflammatory mediators
 High levels:
 Tissue injury by several mechanisms
 Endothelial damage, with thrombosis and increased permeability
 Protease activation and antiprotease inactivation, with a net
increase in breakdown of the ECM
 Direct injury to other cell types

 Various antioxidant - protective mechanisms against this ROS:

Catalase, Superoxide dismutase, and Glutathione
 Chemical Mediators of Inflammation…
 Reactive Nitrogen-oxygen Species (RNOS): Nitric Oxide
(NO)
 Short-lived, soluble, free-radical gas

 Formed by activated macrophages during the oxidation of

arginine by the action of enzyme, NO synthase (NOS)

 NO plays many roles in inflammation including:

 Relaxation of vascular smooth muscle (vasodilation),
 Antagonism of all stages of platelet activation (adhesion,
aggregation, and degranulation)
 Reduction of leukocyte recruitment at inflammatory sites
 Act as a microbicidal (cytotoxic) agent (with or without
superoxide radicals) in activated macrophages.
Role of Nitric
oxide in
vascular
smooth
muscle
relaxation,
vasodilation
and
cytotoxicity
Clinical Comment on Parkinson’s Disease
A model for the role of ROS and RNOS in
neuronal degradation in Parkinson’s disease.
1. Dopamine levels are reduced by monoamine oxidase,
which generates H2O2.
2. Superoxide O2- also can be produced by mitochondria,
which SOD will convert to H2O2. Iron levels increase,
which allows the Fenton reaction to proceed,
generating hydroxyl radicals OH .
3. NO, produced by inducible nitric oxide synthase, reacts
with superoxide to form RNOS.
4. The RNOS and hydroxyl radical lead to radical chain
reactions that result in lipid peroxidation, protein
oxidation, the formation of lipofuscin, and neuronal
degeneration. The end result is a reduced production
and release of dopamine in Parkinson’s disease, a
decrease in the amount of dopamine reaching the
basal ganglia leads to the clinical symptoms observed
( resting tremors of the hand, which disappears on
using it for doing a purposeful movement).
 Chemical Mediators of Inflammation…
Ethanol and Free Radical Formation
 Increased oxidative stress in the liver during chronic ethanol
intoxication arises from increased production of free radicals,
principally by CYP2E1 (Cytochrome P450 Family 2 Subfamily E
Member 1)

 The hydroxyethyl radical (CH3CH2O.) is produced during

ethanol metabolism and can be released as a free radical
 Phospholipids, the major lipid in cellular membranes, are a
primary target of peroxidation caused by free radical release
 Peroxidation of lipids in the inner mitochondrial membrane
may contribute to the inhibition of electron transport and
uncoupling of mitochondria, leading to inflammation and
cellular necrosis
 Induction of CYP2E1 and other P450 cytochromes also
increases formation of other radicals and the activation of
hepatocarcinogens
 Chemical Mediators of Inflammation…
 Neuropeptides
 Initiate inflammatory responses
 Small proteins, such as substance P
 Transmit pain signals, regulate vessel tone, and modulate
vascular permeability
 Prominent in the lung and gastrointestinal tract
2. Plasma-protein-derived mediators
 Circulating proteins of three interrelated systems - the
complement, kinin, clotting and fibrinolytic systems
 Inactive precursors that are activated at the site of
inflammation – action of enzyme.
 Each of these systems has its inhibitors and accelerators in
plasma - negative and positive feedback mechanisms
respectively.
 Hageman factor (factor XII) of clotting system – a key role in
interactions of the four systems.
 Chemical Mediators of Inflammation…
Purine degradation and Inflammation
 Purines, when degraded, cannot generate energy, nor can the
purine ring be substantially modified.

 The end product of purine ring degradation is uric acid, which is

excreted in the urine.

 Uric acid has a limited solubility, and if it were to accumulate, uric

acid crystals would precipitate in tissues of the body with a
reduced temperature.

 This condition of acute painful inflammation of specific soft

tissues and joints is called gout.

 Pyrimidines, when degraded, however, give rise to water-soluble

compounds, such as urea, carbon dioxide, and water and do not
lead to a disease state if pyrimidine catabolism is increased.
 Chemical Mediators of Inflammation…
Metabolic Syndrome and Inflammation
 Abdominal obesity is associated with a cluster of metabolic
abnormalities that is referred to as the metabolic syndrome and
includes:
 Glucose intolerance (hyperglycemia in the case of diabetes)
 Hyperinsulinemia
 Dyslipidemia (low levels of high-density lipoprotein and elevated
TAGs), and
 Hypertension
 Nonalcoholic fatty liver disease

 The metabolic syndrome is also associated with a state of low-

grade, chronic, systemic inflammation that contributes to the
pathogenesis of insulin resistance (T2D) and atherosclerosis
 Chemical Mediators of Inflammation…
Metabolic Syndrome and Inflammation…
 In obesity, adipocytes release pro-inflammatory mediators such as
IL-6 and induces inflammation

 Additionally, low levels of the adipocyte hormone adiponectin

may trigger inflammation

 Obese
 (IL-6 plays roles
people havein chronic inflammation:
low adiponectin levelschronic inflammatory
and this has been
diseases
linked (autoimmune
to various types ofdiseases
metabolicandabnormalities
cancer) and even in the
(metabolic
cytokine storm of corona virus disease 2019 (COVID-19))
Syndromes)