Role of growth factors, cytokines, and their receptors in the pathogenesis of psoriasis.

ABSTRACT

Psoriasis is characterized by epidermal hyperplasia, altered epidermal maturation, and local accumulation of acute and chronic inflammatory cells. Keratinocyte hyperplasia in psoriasis may be explained in part by overproduction of growth factors or cytokines which stimulate epidermal proliferation and by altered metabolism of growth-factor receptors in affected skin. Psoriatic epidermis displays overproduction of TGF-alpha and interleukin-6 (IL-6), factors produced by keratinocytes and other cell types in psoriatic skin. TGF-alpha and IL-6 are mitogens for normal human keratinocytes and act via specific receptors. The TGF-alpha receptor (EGF receptor) is overexpressed in psoriatic epithelium and its altered expression could be caused in part by gamma interferon which prevents normal receptor down-regulation in response to EGF binding. Several phenotypic features of the psoriatic keratinocyte, including growth activation and expression of HLA-DR, gamma-IP-10, ICAM-1, and other molecules, are best explained as resulting from the combined effects of TGF-alpha, IL-6, and gamma interferon (and possibly other cytokines) on epidermal keratinocytes. The multiple histologic features of psoriasis, including epidermal hyperplasia and accumulation of acute and chronic inflammatory cells, may be mediated by defined growth factors and cytokines that are produced in psoriatic skin and affect the function of diverse cell types.