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Psoriasis Treatment By Anogen

Psoriasis Treatment By Anogen

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Published by Anogen
Abcream: A topical treatment of psoriasis with monoclonal antibodies that neutralize interleukin 8 (IL-8) by Anogen.
Abcream: A topical treatment of psoriasis with monoclonal antibodies that neutralize interleukin 8 (IL-8) by Anogen.

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Categories:Types, Research
Published by: Anogen on Jan 14, 2013
Copyright:Attribution Non-commercial

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01/14/2013

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1 |Page 
Abcream
A topical treatment of psoriasis with monoclonal antibodiesthat neutralize interleukin 8 (IL-8)
1. Introduction:
Psoriasis is a chronic, inflammatory dermatitis induced by multiple factors that affects peoplewith a specific genetic background. The incidence of the disease varies by population.According to the National Institute of Health (NIH), approximately 2.2% of the United States population is affected by psoriasis. Internationally, the incidence of psoriasis is approximately120-180 million people. The rates of incidence for various nations/regions are as follows:Scandinavia 7-8%
Denmark 5-6%
Germany 4%
Canada 2-3%
Russia 2-3%
 NorthernEurope 2-3%
Great Britain 2%
China 0.47%
and Kuwait 0.11%.It is interesting to note that the more developed the country, the higher percentage of peopleaffected by psoriasis. About 4% of the population in the most developed countries suffers from psoriasis. Some exceptions are Japan and Australia.The etiology of psoriasis might involve the over-expression of a number of cytokines, amongwhich Interleukin-8 (IL-8) plays a pivotal role. Research has shown that IL-8 levels could elevate100-fold in psoriasis-affected tissue when compared to normal skin tissue. In addition tocontributing to the inflammation process, IL-8 is also a growth factor for skin cells that proliferatein psoriatic tissue. Finally, IL-8 is a potent angiogenesis factor, so it may contribute to theingrowth of blood vessels that nourish psoriatic tissue.Based on these findings, Anogen-Yes Biotech Laboratories Ltd. was the first company in theworld to carry out the research and development of the revolutionary anti-IL-8 treatment of  psoriasis in 1993. Abcream (Anti-IL-8 monoclonal antibody topical cream) reverses theinflammatory pathological changes by neutralizing the excessive IL-8 in the psoriatic tissue andother skin conditions.
2.
 
The pharmacological mechanism
2.1.
 
The biological functions of interleukin-8 (IL-8):Interleukin-8
IL-8) is a member of the chemokine superfamily with 72 residues (MW=8,000).Interleukin-8 has been cited as a pro-inflammatory mediator in gingivitis and psoriasis. IL-8acts as neutrophil activator and chemotactic factor. In particular, there is compelling evidenceshowing that IL-8 plays a pivotal role in the inflammatory process. IL-8 is secreted by severalcell types, including macrophage, neutrophil, monocyte, endothelial cells, keratinocyte etc., andaffects the cells to induce inflammatory response.Most likely, the effect of IL-8 in promoting or causing tissue damage is by inducing theinfiltration of neutrophilic leukocytes as well as by triggering the release of lysosomal enzymesand superoxide anions from leukocytes. The excess amount of IL-8 level in affected tissues
 
2 |Page 
has been found to be associated with a number of disease states. Among these diseases are psoriasis
arthritis deformans, idiopathic fibrosis of the lung, enteritis
adult respiratorydistress syndrome, and septic shock etc.2.2.
 
The association of IL-8 over expression with psoriasis:Psoriasis is characterized by abnormal keratinocyte growth and differentiation. The functionalabnormality of keratinocytes is believed to be triggered by T lymphocytes, and variouscytokines. In addition, polymorphonuclear neutrophil (PMN) infiltration of the skin andMunro microabscesses are characteristic histological findings in psoriasis, confirming thatneutrophils have a role in the pathogenesis of this disease. It has been postulated that inaddition to influencing keratinocyte growth and differentiation of neutrophils in the epidermis,IL-8 might also trigger T-lymphocyte activation by inducing cell-surface expression of HLA-Dr.The accumulation of neutrophils in the outermost layer of the epidermis has been associatedwith the presence of highly inflammatory, treatment-refractory psoriasis plaques.IL-8 plays a crucial role in the pathogenesis of psoriasis:2.2.1.
 
IL-8 is a strong chemotactic factor. IL-8 over-expression in the skin gathers largeamount of neutrophils, T-lymphocytes and other inflammatory cells. Theinfiltration of these cells damages skin tissue and causes blisters. The gatheredneutrophils and T-lymphocytes also produce large amount of IL-8 and aggravatelocal pathological changes, resulting in inflammation of skin and accumulation of debris and scales formed by necrotic cells and dead tissue.2.2.2.
 
IL-8 is a strong growth factor of epidermal cells. Excessive amount of IL-8 production can lead to the overgrowth of abnormal keratinocytes in the focus of  psoriasis.2.2.3.
 
IL-8 is also a potent angiogenesis factor. It causes the acceleration of blood vesselformation in psoriatic focus, making possible sufficient blood supply for theabnormal growth and proliferation of epidermal cells.2.2.4.
 
The biological effect of IL-8 is mediated by its receptors on the surface of theinflammatory cells. Both keratinocyte in the focal zone and the infiltratedneutrophilic leukocyte can express large amount of IL-8 receptors on their surface.Increased numbers of IL-8 receptors and elevated IL-8 can lead to severe dermatitisin the vicious cycle.2.3. The therapeutic effects of anti-human IL-8 monoclonal antibody on psoriasis:The monoclonal antibody is a high titer neutralization antibody specific to IL-8. It can make aneffective therapy to psoriasis by neutralizing excessive IL-8 production and eliminatingneutrophil recruitment, thus, possessing anti-inflammatory role at the psoriatic skin. In addition,the antibody can block IL-8’s angiogenic effect. Therefore, local microvascular formation andthe abnormal proliferation, differentiation, and necrosis of keratinocytes can be controlled. As atotal result, the symptoms of psoriasis can be reduced.
 
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2.4. The Specificity of this anti-IL-8 monoclonal antibody:The specificity of this anti-IL-8 antibody was tested by measuring the cross-reactivity of thisantibody with other cytokines, chemotactic factors and cytokines that share structural similaritywith IL-8. The results (Table 1 & 2) showed that the anti-IL-8 monoclonal antibody washighly specific to IL-8, and had no cross-reactivity with following factors: GM-CSF, TGF-
β
,MCAF, TNF-
α
, IL-7, IL-1
β
, b-FGF, IL-16, MCP-3, M-CSF, EGF, and GRO
α
, PF-4, ENA78,GCP2. The following results were from 2 ELISA assays:Table 1. Test the cross-reactivity with other cytokines and chemotactic factors.
Cytokine OD readingIL-8 Over reading range (>2.7)GM-CSF 0.037TGF-

0.021MCAF 0.023TNF-

0.039IL-7 0.060IL-1

0.029b-FGF 0.027IL-16 0.044MCP-3 0.024MCSF 0.044EGF 0.044BSA 0.147HAS 0.129

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