Interleukin 1 receptor antagonist in human epidermis and cultured keratinocytes

Abstract

Interleukin 1 (IL‐1), present in high amounts in normal human skin without any sign of inflammation, suggests a complex mechanism by which its bioactivity is regulated. The specific receptor antagonist of IL‐1 (IL‐1ra) was analyzed in human skin, sweat and cultured keratinocytes. Extracts of both skin and cultured keratinocytes blocked the binding of [¹²⁵I]IL‐1 to its receptor whereas sweat did not. The inhibitory activity was cell‐associated, was not secreted by cultured keratinocytes, and IL‐1ra mRNA was identified in these cells. There was an inverse relationship between the level of IL‐1ra and that of IL‐1α and β since extracts of differentiating keratinocytes (DK) and higher IL‐1ra levels and expressed more mRNA for IL‐1ra than non‐differentiated keratinocytes (NDK), whereas NDK contained 4 times more IL‐1α and β proteins than DK. This association of cell differentiation with a shift in agonist/antagonist ratio might be related to important autocrine or paracrine functions of IL‐1 in normal and inflamed human skin.