Normal sexual function in male mice lacking a functional type I interleukin-1 (IL-1) receptor

Previous studies have shown that macrophages and their cytokine products, particularly interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha), regulate testicular Leydig cell steroidogenesis in vitro and in vivo. However, the data concerning IL-1 have been somewhat contradictory, showing both inhibitory and stimulatory effects of IL-1 depending on the experimental conditions. In the present studies, mice lacking a functional type I IL-1 receptor (IL-1R]; the only IL-1 receptor subtype capable of IL-1-induced signal transduction) were used to examine the role of this cytokine in vivo. The data show that the absence of IL-1 signal transduction has no effect on steroidogenic enzyme concentrations within the Leydig cells, and the males have normal serum testosterone concentrations. Moreover, epididymal sperm numbers are normal in IL-1RI nullizygous males in contrast to recent reports of a role for IL-1 in germ cell proliferation and DNA synthesis. Taken together these observations suggest that IL-1 signalling is not essential for Leydig cell function or spermatogenesis in vivo and highlight the need to reassess many of the current methods of experimental approaches for examining cytokine function in vitro.