IL-6 KNOCK-OUT MICE SHOW MODIFIED BASAL IMMUNE FUNCTIONS, BUT NORMAL IMMUNE-RESPONSES TO STRESS

To better determine the role of interleukin-6 in the mechanisms that r egulate stress-induced immunosuppression, we used in this study an int erleukin-6-deficient mice model recently generated by gene targeting. We report here that, in basal conditions, mutant mice are characterize d by altered immune functions. Natural killer activity and interleukin -2 production are lower in splenocytes of interleukin-6 deficient mice compared to those of controls, whereas Concanavalin A-induced splenoc yte proliferation is comparable with that observed in wild-type mice. Moreover, splenocyte concentrations of the immunosuppressive opioid pe ptide beta-endorphin are higher in interleukin-6 deficient mice while serum Corticosterone concentrations are unchanged. After exposure to 1 6 h of restraint stress, a significant suppression of the immune param eters is exhibited and a significant increase of splenocyte beta-endor phin concentrations are present in knock-out and normal animals. Final ly, corticosterone is normally induced in stressed interleukin-6-defic ient mice, thus demonstrating that interleukin-6 is not crucial for th e activation of the hypothalamic-pituitary-adrenal axis. In conclusion , our results indicate that interleukin-6 is not a key factor in the i mmunosuppression observed after restraint stress, (C) 1998 Academic Pr ess.