Regulation of Sertoli cell IL-1 and IL-6 production in vitro.

Interleukin-1 (IL-1) and IL-6 are pleiotropic cytokines produced by a large variety of cell types. In the testis, Sertoli cells produce IL-1alpha and IL-6. Previous studies have demonstrated that, in vitro, Sertoli cell IL-1alpha production is stimulated by some inducers of macrophage IL-1, as well as by phagocytosis of residual bodies. Furthermore, we have also shown that IL-1alpha is able to enhance Sertoli cell IL-6 production by an autocrine action. The aim of the present study was to further investigate the regulation of Sertoli cell IL-1 and IL-6 production. Three categories of potential regulators were tested; the lipopolysaccharide (LPS) and the yeast extract zymosan; follicle stimulating hormone (FSH), testosterone and dexamethasone; tumor necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma) and the nerve growth factor beta (NGFbeta). It was found that zymosan (400-800 microg/ml) and LPS (20 microg/ml) stimulated Sertoli cell IL-1 and IL-6 production. FSH (1 x 10(-2)-1 microg/ml) and NGF (25-200 ug/ml) stimulated Sertoli cell IL-6 levels in a dose-dependent manner but had no effect on IL-1. The effect of testosterone on Sertoli cell IL-1 and IL-6 secretion was biphasic: dramatic increased secretion with low concentrations (0.01-1 nM) and no effect with the higher concentration tested (100 nM). Dexamethasone reduced LPS-induced IL-1 and IL-6 production in a concentration-responsive manner (0.04-0.4 and 0.4-40 ng/ml, respectively). Addition of TNFalpha to Sertoli cells resulted in a dose-dependent increase of both cytokines (50-100 U/ml for IL-1, 100-200 U/ml for IL-6). In the case of IFNgamma, intermediate concentrations (50-100 U/ml) stimulated IL-1alpha, whereas the highest concentrations (200-400 U/ml) inhibited IL-6. It is concluded that regulation of Sertoli cell IL-1 and IL-6 is very complex as it involves factors as different as hormones, paracrine factors and activators of macrophages. The latter agents may be mimicking the action of pathogens or the action of intratesticular agents whose nature remains to be elucidated.