Document Detail

Central administration of rat IL-6 induces HPA activation and fever but not sickness behavior in rats.
MedLine Citation:
PMID:  10070124     Owner:  NLM     Status:  MEDLINE    
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.
M J Lenczowski; R M Bluthé; J Roth; G S Rees; D A Rushforth; A M van Dam; F J Tilders; R Dantzer; N J Rothwell; G N Luheshi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  276     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-04-15     Completed Date:  1999-04-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  R652-8     Citation Subset:  IM    
Department of Pharmacology, Faculty of Medicine, Research Institute Neurosciences Vrije Universiteit, Graduate School Neurosciences Amsterdam, 1081 BT Amsterdam, The Netherlands.
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MeSH Terms
Adrenocorticotropic Hormone / blood
Behavior, Animal / drug effects*
Body Temperature / drug effects
Corticosterone / blood
Fever / chemically induced*
Hypothalamo-Hypophyseal System / drug effects,  physiology*
Injections, Intraventricular
Interleukin-6 / pharmacology*
Motor Activity / drug effects
Pituitary-Adrenal System / drug effects,  physiology*
Rats, Wistar
Recombinant Proteins
Social Behavior
Reg. No./Substance:
0/Interleukin-6; 0/Recombinant Proteins; 50-22-6/Corticosterone; 9002-60-2/Adrenocorticotropic Hormone

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