Roles of interleukin-1 alpha and -1 beta in endotoxin-induced suppression of plasma gonadotropin levels in rats.

Using specific antagonists to rat interleukin (IL)-1 alpha and IL-1 beta, the roles of these IL-1s in endotoxin-induced suppression of plasma gonadotropin levels in freely-moving rats were studied. In orchiectomized rats, recombinant rat IL-1 alpha and IL-1 beta administered into the lateral ventricles almost equipotently suppressed plasma LH levels. Twenty five micrograms of bacterial endotoxin or lipopolysaccharide (LPS) administered similarly showed a comparable effect as that of 1 microgram IL-1 alpha or IL-1 beta, and completely lowered plasma LH levels by 60 min after the injection. To examine the roles of endogenous IL-1 alpha and IL-1 beta, anti-rat IL-1 alpha antiserum (anti-IL-1 alpha) and a recombinant human IL-1 receptor antagonist (IL-1ra) were used as specific blockers for IL-1 alpha and IL-1 beta, respectively. Anti-IL-1 alpha (10 microliters) or IL-1ra (10 micrograms) administered intracerebroventricularly (icv) with 25 micrograms LPS, significantly attenuated the LPS-induced effect on plasma LH levels during the first 60 min after LPS infusion, but not during the second 60 min. LPS at a dose of 5 micrograms induced smaller but still significant changes in plasma LH levels compared with 25 micrograms LPS or 1 microgram IL-1 beta. IL-1ra (10 micrograms) completely blocked LH suppression induced by 1 microgram IL-1 beta, but did not completely reverse the changes of LH induced by 5 micrograms LPS. IL-1ra injected iv also significantly attenuated the early suppressive effect of iv administered LPS, but not its late effect on plasma LH levels. However, iv administered IL-1ra had no influence on the effects of icv administered LPS. These data indicate that at least a part of plasma LH suppression caused by icv administered LPS is mediated via IL-1 alpha and IL-1 beta synthesized within the brain, while factor(s) other than IL-1 also participate in the LPS-induced change, particularly during the later period. A similar mechanism may also work peripherally in the case of iv administered LPS-induced plasma LH suppression.