CYTOKINES DERIVED FROM ACTIVATED HUMAN MONONUCLEAR-CELLS MARKEDLY STIMULATE TRANSFERRIN SECRETION BY CULTURED SERTOLI CELLS

There is considerable evidence that Sertoli cell function is controlle d not only by hormones, but also by locally produced growth factors an d cytokines. To gain more insight into the nature and effects of cytok ines potentially involved in the control of Sertoli cell function, we incubated rat Sertoli cells with media conditioned by activated human peripheral blood mononuclear cells. Such media (PBMC-CM) are known to be an extremely rich source of a variety of cytokines. It was demonstr ated that PBMC-CM and protein fractions derived from them stimulate Se rtoli cell transferrin secretion and messenger RNA production more pot ently than peritubular cell-conditioned medium or FIRT (a combination of FSH, insulin, retinol, and testosterone). Transferrin secretion exp ressed per mg cell DNA was stimulated approximately 5-fold by peritubu lar cell-conditioned medium or FIRT and nearly 20-fold by PBMC-CM. The effects of PBMC-CM were accompanied by a limited increase in cAMP and a noticeable rise in cGMP. Affinity chromatography on a column coated with an antiserum directed against interleukin-1 beta (IL 1 beta) sho wed that part of the activity in the PBMC-CM was related to IL-1 beta. The remainder of the activity was largely retained by an affinity col umn coated with an antiserum that recognizes IL-6 and a number of othe r known and unknown cytokines. Purified IL-1 beta provoked a 2- to 3-f old stimulation of Sertoli cell transferrin secretion. Moro limited st imulatory effects were observed with IL-6. Neither of these cytokines or their combination approached the degree of stimulation observed wit h crude PBMC-CM, suggesting that other cytokines are involved. It is c oncluded that the mixture of cytokines present in PBMC-CM is a more po werful stimulator of Sertoli cell transferrin secretion than any other agonist known at the present time, IL-1 and IL-6 may be responsible f or part of the observed effects, but one or more other cytokines are p robably involved.