Central administration of rat IL-6 induces HPA activation and fever but not sickness behavior in rats

Interleukin (IL)-6 has been proposed to mediate several sickness responses, including brain-mediated neuroendocrine, temperature, and behavioral chang es. However, the exact mechanisms and sites of action of IL-6 are still poo rly understood. In the present study, we describe the effects of central ad ministration of species-homologous recombinant rat IL-6 (rrIL-6) on the ind uction of hypothalamic-pituitary-adrenal (HPA) activity, fever, social inve stigatory behavior, and immobility. After intracerebroventricular administr ation of rrIL-6 (50 or 100 ng/rat), rats demonstrated HPA and febrile respo nses. In contrast, rrIL-6 alone did not induce changes in social investigat ory and locomotor behavior at doses of up to 400 ng/rat. Coadministration o f rrIL-6 (100 ng/rat) and rrIL-1 beta (40 ng/rat), which alone did not affe ct the behavioral responses, reduced social investigatory behavior and incr eased the duration of immobility. Compared with rhIL-6, intracerebroventric ular administration of rrIL-6 (100 ng/rat) induced higher HPA responses and early-phase febrile responses. This is consistent with a higher potency of rrIL-6, compared with rhIL-6, in the murine B9 bioassay. We conclude that species-homologous rrIL-6 alone can act in the brain to induce HPA and febr ile responses, whereas it only reduces social investigatory behavior and lo comotor activity in the presence of IL-1 beta.