THE EFFECTS OF INTERLEUKIN-10 ON INTERLEUKIN-1 RECEPTOR ANTAGONIST AND INTERLEUKIN-1-BETA PRODUCTION IN HUMAN MONOCYTES AND NEUTROPHILS

LPS stimulates human monocytes and neutrophils to produce IL-1 beta an d IL-1 receptor antagonist (IL-1ra). IL-10 has been shown to inhibit L PS-induced IL-1 beta production in human monocytes. The objective of t hese studies was to examine the effects of IL-10 on human monocyte and neutrophil IL-1ra protein and mRNA production and compare it to IL-1 beta. IL-10 markedly inhibited LPS-induced IL-1 beta mRNA and protein production in both cell types. IL-10 alone induced IL-1ra mRNA product ion in monocytes with a low level of protein production. Furthermore, IL-10 led to enhanced levels of IL-1ra mRNA in LPS-induced monocytes a t 2 to 6 h and of IL-1ra protein at 4-16 h, but there was no increase in levels of IL-1ra protein at 24 h or later. In neutrophils IL-10 alo ne did not stimulate IL-1ra protein or mRNA production and did not aug ment LPS-induced IL-1ra mRNA. These net effects of IL-10 resulted in a n increase in the ratio of IL-1ra to IL-1 beta in both neutrophils and monocytes. The net effects of IL-10 on inflammatory cells may be impo rtant in modulation of biologic responses to IL-1.