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

M. J.P. Lenczowski, R. M. Bluthé, J. Roth, G. S. Rees, D. A. Rushforth, A. M. Van Dam, F. J.H. Tilders, R. Dantzer, N. J. Rothwell, G. N. Luheshi

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Interleukin (IL)-6 has been proposed to mediate several sickness responses, including brain-mediated neuroendocrine, temperature, and behavioral changes. However, the exact mechanisms and sites of action of IL- 6 are still poorly understood. In the present study, we describe the effects of central administration of species-homologous recombinant rat IL-6 (rrIL- 6) on the induction of hypothalamic-pituitary-adrenal (HPA) activity, fever, social investigatory behavior, and immobility. After intracerebroventricular administration of rrIL-6 (50 or 100 ng/rat), rats demonstrated HPA and febrile responses. In contrast, rrIL-6 alone did not induce changes in social investigatory and locomotor behavior at doses of up to 400 ng/rat. Coadministration of rrIL-6 (100 ng/rat) and rrIL-1β (40 ng/rat), which alone did not affect the behavioral responses, reduced social investigatory behavior and increased the duration of immobility. Compared with rhIL-6, intracerebroventricular 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 febrile responses, whereas it only reduces social investigatory behavior and locomotor activity in the presence of IL-1β.

Original languageEnglish
Pages (from-to)R652-R658
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3 45-3
Publication statusPublished - Mar 1999


  • Adrenocorticotropic hormone
  • Brain
  • Corticosterone
  • Hypothalamic-pituitary-adrenal activation
  • Interleukin- 6
  • Interleukin-1β
  • Locomotor behavior
  • Social behavior

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