Epidermal proinflammatory cytokines

We have developed a preliminary kinetic model of the interleukin 1 (IL-1)-stimulated intracellular signaling pathway in epidermal keratinocytes as an initial effort toward the pharmacodynamic modeling of the skin. On exposure to external stimuli, such as chemical irritants, the skin secretes various cytokines and chemo-kines and evokes a cascade of events in the subcutaneous tissue. Therefore, the pharmacodynamic process of the skin primarily involves the responses of the skin cells to these endogenous proteins. Among them, one of central importance is IL-1, a proinflammatory cytokine that mediates the host defense activities of the skin. The model captures the series of biochemical events initiated from IL-1 a binding to IL-1 receptor (type I) on the cell surface that activates the transcriptional factor nuclear factor (NFk-B) and leads to production of a responsive protein, IL-6, as illustrated in Figure 6.6. 

Psoriasis is another chronic and autoimmune skin disorder characterized by raised, scaly, and reddened patches (or plaques), which result from hyperproliferation of the epidermis and inflammation of both epidermal and dermal layers [126]. This disease is also characterized by periods of remissirMi and relapse. Psoriasis is mediated by activated T cells [127] and activated dendritic cells located in psoriatic plaques. These cells release proinflammatory cytokines, including both TNF-a and IFN-y, that increase blood vessel synthesis, vasodilatation, and keratinocyte proliferation [128]. 

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