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Am J Physiol Regul Integr Comp Physiol 276: R652-R658, 1999;
0363-6119/99 $5.00
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Vol. 276, Issue 3, R652-R658, March 1999

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

M. J. P. Lenczowski1, R.-M. Bluthé2, J. Roth3, G. S. Rees4, D. A. Rushforth5, A.-M. van Dam1, F. J. H. Tilders1, R. Dantzer2, N. J. Rothwell5, and G. N. Luheshi5

1 Department of Pharmacology, Faculty of Medicine, Research Institute Neurosciences Vrije Universiteit, Graduate School Neurosciences Amsterdam, 1081 BT Amsterdam, The Netherlands; 2 Institut François Magendie, Institut National de la Recherche Agronomique-Institut National de la Santé et de la Recherche Médicale U394, 33077 Bordeaux Cedex, France; 3 Klinikum Physiologisches Institut, Justus-Liebig Universität Giessen, D-35392 Giessen, Germany; 4 Division of Endocrinology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire EN6 3QG; and 5 School of Biological Sciences, Manchester M13 9PT, United Kingdom

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-1beta (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-1beta .

adrenocorticotropic hormone; corticosterone; interleukin-1beta ; interleukin-6; brain; social behavior; locomotor behavior; hypothalamic-pituitary-adrenal activation


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