ROLES OF INTERLEUKIN-1-ALPHA AND INTERLEUKIN-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-mu-g 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, antirat 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-mu-l) or IL-1ra (10-mu-g) administered intracerebroventricularly (icv) with 25-mu-g 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-mu-g induced smaller but still significant changes in plasma LH levels compared with 25-mu-g LPS or 1-mu-g IL-1-beta, IL-1ra (10-mu-g) completely blocked LH suppression induced by 1-mu-g IL-1-beta, but did not completely reverse the changes of LH induced by 5-mu-g 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.