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.