Cytokines inhibit sexual behavior in female rats: I. Synergistic effects of tumor necrosis factor α and interleukin-1

The secretion of cytokines such as tumor necrosis factor α (TNFα) and interleukin-1 (IL-1) during immune activation induces sickness behavior. We have previously demonstrated that administration of either lipopolysaccharide (LPS) or IL-1 suppresses sexual behavior in female, but not in male rats. In the present study we sought to determine some of the mechanisms that are involved in mediating the alterations of female sexual behavior during immune activation. We report that sexual motivation of estrous females was reduced by intracerebroventricular administration of either recombinant rat (rr)TNFα (7.5 μg/rat) or rrIL-1β (100 ng/rat), whereas sexual receptivity was altered only by IL-1β. A significant reduction of both sexual motivation and receptivity was also induced by the combined administration of subthreshold doses of TNFα (3 μg/rat) and IL-1β (20 ng/rat). These findings indicate that TNFα and IL-1β act synergistically to suppress sexual motivation and receptivity. Moreover, LPS (100 μg/kg, ip)-induced reduction of sexual motivation was antagonized by the combined administration of the TNFα synthesis blocker pentoxifylline (50 mg/kg, ip) and IL-1 receptor antagonist (10 mg/kg, ip), but not by the administration of each of these substances by itself. In contrast, LPS-induced reduction of sexual receptivity was completely prevented by pentoxifylline. These findings indicate that the effects of LPS on sexual motivation are mediated by the synergistic effects of TNFα and IL-1, but only TNFα is required for the effect of LPS on receptivity.