RECOMBINANT MONOCYTE-DERIVED INTERLEUKIN-1 RECEPTOR ANTAGONIST REVERSES INHIBITORY EFFECTS OF INTERLEUKIN-1 ON LEYDIG-CELL STEROIDOGENESIS

Previously we have reported that interleukin-1 (IL-1) is a potent inhibitor of Leydig cell function. Most recently, IL-1 receptor antagonist (IL-1ra) has been purified, sequenced and cloned. In the present study, we evaluated the recombinant monocyte-derived IL-1ra on the inhibitory effects of IL-1. The addition of recombinant human IL-1ra up to 1000 ng/ml has no discernible effects on human chorionic gonadotropin (hCG)-stimulated testosterone formation in primary cultures of rat Leydig cells. Similar to that reported previously, IL-1-beta caused a dose-dependent inhibition of hCG-induced testosterone. The inhibitory effect of IL-1-beta could be reversed by the concomitant addition of IL-1ra. The amounts of IL-1ra required to reverse the effect of IL-1 were 25-fold higher. Our results suggest that IL-1 is important in modulating Leydig cell function and its effect most likely is mediated by specific IL-1 receptors.