Endocrine effects of recombinant interleukin 6 in man

In a phase II study, 5 male patients with a good performance status, who had metastatic renal cell carcinoma, received interleukin 6 (IL-6) to evaluate a possible antitumor effect of the cytokine. This offered the opportunity to investigate endocrine effects of IL-6 in man. The patients were studied the day before (day-1), and on days +1 and +21 of the IL-6 therapy (150 micrograms administered subcutaneously every day at 09.00 h). Blood was sampled at 09.00, 11.00, 13.00, 16.00, and 20.00 h. Compared with day -1, on days +1 and +21 serum levels of IL-6 were substantially elevated between 11.00 and 20.00 h. IL-6 significantly decreased serum thyrotropin (TSH) levels on day +1 (p < 0.05). The decrease was even more pronounced on day +21 when TSH concentrations were persistently below the respective values of day +1, suggesting, in addition to the acute action of IL-6, an effect developing with repeated IL-6 administrations. Total serum T3 and T4 levels were significantly lower on day +21 than on days -1 and +1. In contrast, free T3 and free T4 values did not differ among days -1, +1 and +21. Acutely, IL-6 had no effect on serum luteinizing hormone (LH) concentrations. However, on day +21, averaged serum LH levels (between 11.00 and 20.00 h) were significantly higher (8.4 +/- 1.1 IU/l) than on days -1 (6.5 +/- 0.2 IU/l) and +1 (6.4 +/- 0.4 IU/l). Average serum testosterone levels were slightly but not significantly enhanced on day +21. IL-6 did not influence follicle-stimulating hormone, growth hormone, or prolactin levels, neither acutely nor after 3 weeks of daily administration. The data indicate a modulating effect of IL-6 on secretory activity of different endocrine axes in man.