EVALUATION OF OVARIECTOMY AND DEHYDROEPIANDROSTERONE-SULFATE ADMINISTRATION ON INTERLEUKIN-6 LEVELS AND B16 MELANOMA GROWTH IN MICE

Interleukin-6 (IL-6) can inhibit growth of a variety of tumors includi ng B16 murine melanoma. IL-6 levels increase with age and after ovarie ctomy or menopause. The adrenal androgen, dehydroepiandrosterone sulfa te (DHEAS), can lower serum IL-6 levels in aged mice. Therefore, we hy pothesized that ovariectomy would induce elevations of serum IL-6 capa ble of inhibiting B16 melanoma growth in mice. Additional ly we postul ated that DH EAS would beable to reverse the ovariectomy-induced incre ase in IL-6, thus abrogating IL-6's antitumor effect. To explore our h ypothesis ovariectomy or sham surgery was performed on C57BL/6 mice fo llowed by inoculation with B16 melanoma. The mice then received either oral DHEAS or placebo. Ovariectomy resulted in significant weight gai n without altered food intake. IL-6 levels were elevated comparably in all groups after ovariectomy or sham surgery. Administration of DHEAS had no effect on these parameters. Tumor size was not significantly d ifferent between test groups, however the ovariectomized mice receivin g DHEAS had a trend towards larger tumor volume compared to the other test groups. Additionally, splenocytes from ovariectomized mice receiv ing DHEAS demonstrated enhanced tumor cell killing in vitro. We conclu de that ovariectomy does not elevate serum IL-6 to a level which resul ts in inhibition of B16 tumor cell growth and may in fact enhance tumo r growth in conjunction with DHEAS.