Interleukin 6 modulates lnterleukin-1- and stress-induced activation of the hypothalamic-pituitary-adrenal axis in male rats

This study examined the interaction between interleukin 6 (IL-6) and IL-1 and between IL-6 and stress on the activation of the hypothalamic-pituitary-adrenal (HP A) axis. Coadministration of IL-6 (100 ng/rat) with IL-1 (20 or 100 ng/ rat) resulted in synergistic stimulation of the HPA axis, as determined by increased plasma levels of ACTH and corticosterone (CORT) which were greater in rats that received both cytokines than in rats receiving either cytokine alone. Concomitant administration of IL-6 (100 ng/rat) with exposure to a novelty stressor also synergistically stimulated the activation of the HPA axis, as IL�6-treated rats subjected to novelty stress had greater increases in plasma levels of ACTH and CORT than vehicle-treated rats exposed to novelty stress or rats receiving IL-6 alone. However, concomitant administration of IL-6 (100 ng/rat) did not significantly affect restraint stress induced elevation of plasma levels of ACTH and CORT, although IL-6 tended to prolong restraint stress induced elevation of plasma levels of CORT. These findings indicate a modulatory role for IL-6 stimulated HPA axis activity in response to IL-1 or a novelty psychological stressor, but not for restraint stress.