6 DIFFERENT CYTOKINES THAT SHARE GP130 AS A RECEPTOR SUBUNIT, INDUCE SERUM AMYLOID-A AND POTENTIATE THE INDUCTION OF INTERLEUKIN-6 AND THE ACTIVATION OF THE HYPOTHALAMUS-PITUITARY-ADRENAL AXIS BY INTERLEUKIN-1

Ciliary neurotrophic factor (CNTF) and interleukin-g (IL-6) potentiate the elevation of serum corticosterone induced by suboptimal doses of interleukin-1 (IL-1). CNTF also potentiates IL-1-induced serum IL-6. H ere, we report that four other cytokines (leukemia inhibitory factor [ LIF], oncostatin M [OSM], interleukin-11 and cardiotrophin-1) also pot entiated the elevation of serum corticosterone and IL-6 levels induced by IL-1. Furthermore, all the six cytokines studied induced the acute -phase protein serum amyloid A when administered alone. Because these cytokines differ both in structure and in function, but share gp130 as a subunit of their receptors, these results indicate that signaling t hrough gp130 mediates potentiation of IL-1 activities. The potentiatio n of IL-1-induced serum corticosterone levels is not a consequence of the increased serum IL-6 levels observed after IL-1 administration. In fact, in IL-6 deficient mice, IL-1 increased serum corticosterone to a level comparable to that observed in wild-type mice. Thus, either en dogenous IL-6 does not mediate IL-1-induced corticosterone increase, o r its role may be fulfilled by other cytokines. To the extent that gp1 30-dependent cytokines may serve this role, they may be important feed back regulators of inflammation through the activation of the hypothal amus-pituitary-adrenal axis and the potentiation of acute-phase protei n synthesis. (C) 1996 by The American Society of Hematology.