Background: Cytokines do not only mediate responses to infection, but are also involved in behavioral and physiological responses to psychological stressors. IL-6 has received special attention in relation to the development of posttraumatic stress disorders and depression. Objective: We tested effects of prior injection of rat recombinant IL-6 (rrIL-6) on behaviors induced by the forced swim (FS) stressor, and central and peripheral responses of IL-6 to FS. Methods: Rats were injected intraperitoneally with either rrIL-6 (250 ng/0.5 ml) or equal-volume sterile saline twice within an interval of 24 h. One hour after each injection, the rats were exposed to FS or remained at the home cage (control). Results: Injection of rrIL-6 did not affect immobility, swimming or climbing behaviors during FS compared with the saline control. Although FS was not a significant factor for hypothalamic and midbrain IL-6 mRNA and plasma IL-6 responses, FS with prior administration of rrIL-6 significantly increased hypothalamic IL-6 contents in response to FS compared with the saline injection-FS condition. Conclusions: Our results suggested that stressor alone had no influence on plasma IL-6 levels and IL-6 mRNA expression levels in midbrain and hypothalamus, but administration of rrIL-6 followed by FS significantly increased hypothalamic IL-6. Our results support the notion that the interaction between IL-6 and stressor might have implications for the pathophysiology of IL-6-induced depressive symptoms.

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