INTERLEUKIN-1 RECEPTOR ANTAGONIST IN HUMAN EPIDERMIS AND CULTURED KERATINOCYTES

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-1 ra) was analyzed in human skin, sweat and cultured keratinocytes. Extracts of both skin and cultured keratinocytes blocked the binding of [I-125]IL-1 to its receptor whereas sweat did not. The inhibitory activity was cell-associated, was not secreted by cultured keratinocytes, and IL-1 ra mRNA was identified in these cells. There was an inverse relationship between the level of IL-1 ra and that of IL-1-alpha and beta since extracts of differentiating keratinocytes (DK) and higher IL-1 ra levels and expressed more mRNA for IL-1 ra than non-differentiated keratinocytes (NDK), whereas NDK contained 4 times more IL-1-alpha and beta-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.