EFFECT OF GONADAL-STEROIDS ON THE PRODUCTION OF IL-1 AND IL-6 BY BLOOD MONONUCLEAR-CELLS INVITRO

Sex hormones have profound effects on immune responses and may influen ce the outcome of autoimmune diseases such as rheumatoid arthritis (RA ). We investigated the effect of gonadal steroids on the production of interleukin-1 (IL-1) and IL-6, cytokines believed to be important in the pathogenesis of RA. Peripheral blood mononuclear cells (PBMCs) wer e isolated from healthy male donors and male patients with RA, and wer e stimulated with lipopolysaccharide (LPS) in the presence of differen t concentrations of 17-beta-estradiol, progesterone or testosterone. I n studies of cells from normal male donors, 17-beta-estradiol at pharm acological concentrations (greater-than-or-equal-to 10(-6) M) enhanced IL-1 and IL-6 secretion as well as the production of cell-associated IL-1. Progesterone and testosterone at similar concentrations inhibite d IL-1 secretion but had no significant effect on IL-6 secretion or on the production of cell-associated IL-1. In studies of male RA donors, 17-beta-estradiol failed to enhance IL-1 or IL-6 secretion and proges terone failed to inhibit IL-1 secretion. The inhibitory effects of tes tosterone, however appeared to be similar to that in normal donors. It is suggested that 17-beta-estradiol may promote IL-1 and IL-6 product ion and release, while gestation hormone, progesterone, and testostero ne may inhibit IL-1 release in vivo. These data may partly explain the gender and age differences in the incidence of RA and the development of the disease in men with low androgen levels.