Human Leydig cells and Sertoli cells are producers of interleukins-1 and -6

Interleukins (IL)-1 and -6 have been shown to be produced by several categories of cells in the rat testis and involved in the paracrine control of testicular function. Evidence of high amounts of IL-1 have been shown in the human testis, but nothing is known about its cellular origin. Furthermore, to our knowledge, the presence of IL-6 in the human testis has not yet been investigated. Therefore, the present study was aimed at identifying IL-1 and -6 expression and production within the human testis, using RT-PCR, bioassays, and enzyme linked immunosorbent assays. We demonstrated that IL-1 and -6 messenger RNA and proteins were produced constitutively in vitro by human Leydig cell- and Sertoli cell-enriched preparations. FSH only stimulated IL-6 production by Sertoli cell-enriched preparations, but increased the release of both IL-1 and -6 in germ cell-depleted Sertoli cell cultures. In addition, lipopolysaccharides and latex beads enhanced the production of both cytokines by Sertoli cell cultures, whereas human chorionic gonadotropin and lipopolysaccharides enhanced the release of both cytokines by Leydig cells. Enzyme linked immunosorbent assays and neutralization experiments revealed that human Sertoli cells produce essentially the alpha form of IL-1, whereas both forms, alpha and beta, are present in Leydig cells. The demonstration that human Leydig and Sertoli cells produce IL-1 and -6 under the control of gonadotropin hormones and exogenous factors, opens the possibility to study the involvement of these cytokines in the control of testis function, in normal and pathological conditions in men.