Reduced adrenal response to bacterial lipopolysaccharide in interleukin-6-deficient mice

Administration of bacterial lipopolysaccharide (LPS) in rodents induces the release of pro-inflammatory cytokines [tumor necrosis factor (TNF), interl eukin (IL)-1, IL-6] and of ACTH and corticosterone. IL-6 is probably an imp ortant cytokine in the interaction between the immune system and the hypoth alamus-pituitary-adrenal (HPA) axis, but so far the role of IL-6 in lipopol ysaccharide (LPS)-induced HPA activation has not been established unequivoc ally. We examined the effects of intraperitoneal administration of LPS (ran ge 0.25-2000 mug/mouse) on plasma corticosterone, TNF alpha and IL-1 alpha levels in IL-6-deficient (IL-6 -/-) and wildtype control (IL-6 +/+) mice. P lasma corticosterone levels increased within one hour in both mouse strains . The corticosterone response was significantly reduced in IL-6 -/- mice, b ut no differences in TNF alpha or in IL-1 alpha plasma levels were found be tween the two strains. Next, we studied the involvement of IL-1 alpha or TN F alpha in the responses to LIPS in IL-6 -/- and IL-6 +/+ mice by infusion of recombinant human IL-1 receptor antagonist (IL-1 alpha), or by injection of anti-TNF alpha antibodies. Pretreatment with IL-1 alpha or with anti-TN F alpha did not affect the corticosterone response to LPS, neither in IL-6 -/-, nor in IL-6 +/+ mice. Our data suggest that in the stimulation of the HPA axis by LPS in mice blockade of either IL-1 alpha or TNF alpha may be c ompensated for by other mediators. The reduced adrenal response after LPS a dministration found in IL-6 -/- mice indicates a distinct role for IL-6 in the activation of the HPA axis by LIPS. (C) 2001, Editrice Kurtis.