Synergism between interleukin-6 and interleukin-1 beta in hypothalamic serotonin release: a reverse in vivo microdialysis study in F344 rats

The effects of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) perf used locally into the anterior hypothalamus (AHY) on serotonin (5-hydroxytr yptamine, 5-HT) release were investigated in the same region using lit vivo microdialysis in conscious, freely moving F344 rats. IL-1 beta (1 ng/rat) or IL-6 (50 ng/rat) injected directly into the AHY elicited a rapid and tra nsient statistically significant increase in extracellular 5-HT levels (to 161% and 145% of the respective AUC (area under the curve) basal value, 100 %). Intra-hypothalamic infusion of IL-l-receptor antagonist IL-1Ra (2 mu g/ rat) prevented this effect of IL-1 beta, but not that of IL-6, suggesting a n IL-1 beta-independent mechanism for hypothalamic 5-HT release by this lat ter cytokine, Furthermore, intra-hypothalamic co-perfusion of IL-6 with IL- 1 beta at sub-optimal doses (10 ng/rat and 0.5 ng/rat, respectively) synerg ized in releasing hypothalamic 5-HT, thus providing in vivo evidence that b oth cytokines, IL-6 and IL-1 beta are able to modulate the neuronal 5-HT re sponse in the rat AHY.