The Interleukin-1 axis and cutaneous inflammation

Abstract

Since the discovery that epidermal cell-derived thymocyte-activating factor was identical to interleukin (IL)-1α and -β in 1986, these molecules have been implicated in the pathogenesis of skin diseases. In 1995, it has become clear that a group of gene products function to regulate the activity of IL-1. IL-1α and mature 17-kD IL-1β (cleaved from precursor by IL-1β-converting enzyme) bind to the type 1 IL-1 receptor to transduce a signal. This process can be antagonized at the level of the receptor by two distinct forms of the IL-1 receptor antagonist, which bind to the type I receptor but do not transduce a signal. The process can also be antagonized at the level of the ligand by either cell-bound or soluble type 2 IL-1 receptor. This type 2 IL-1 receptor binds ligand but does not transduce a signal Keratinocytes can make each of these variables in vitro, and the balance between agonists and antagonists dictates the biologic outcome of a putative IL-1-mediated event. - Transgenic mice that overexpress - each of these factors individually in epidermis will be useful for enhancing our understanding of the cutaneous biology of IL-1.