The febrile response to tissue inflammation involves both
peripheral and brain il-1 and tnf-[alpha] in the rat.
Luheshi, G N, A Stefferl, A V Turnbull, M J Dascombe, S Brouwer, S J
Hopkins, and N J Rothwell.
School of Biological Sciences, 1.124, University of Manchester,
Oxford Road, Manchester M13 9PT, U.K., Department of Rheumatology,
Hope Hospital, Salford, Manchester M6 8HD, U.K. and The Clayton
Foundation for Peptide Biology, Salk Institute, La Jolla, CA 92137,
USA
APStracts 3:0375R, 1996.
We investigated the role and interaction between TNF-[alpha], IL-1 and
IL-6 in the development of fever, and their involvement in brain and
systemic pathways in response to localised tissue inflammation caused
by injection of turpentine (PS) in the rat. Intramuscular injection
of 10[mu]l TPS caused significant increases in body temperature, of
up to 2 degrees C, when compared to saline treated animals. Fevers
were maximal 7-8h after injection and were preceded by significant
increases in plasma bioactive IL-6. No changes in circulating
bioactive IL-1 or TNF-[alpha] were detected. Systemic injection of
IL-1 receptor antagonist (IL-1ra, 2mg/kg, ip) or anti-TNF-[alpha]
antiserum (0.4ml, iv) almost completely abolished the febrile
responses to TPS over 8h, and markedly inhibited the rise in plasma
IL-6 bioactivity measured 6h after TPS. To test the involvement of
brain cytokines anti-TNF-[alpha] antiserum and IL-1ra were injected
intracerebroventricularly (icv). Injections of anti-TNF-[alpha]
antiserum (3[mu]l/rat, icv) or IL-1ra (400[mu]g/kg, icv)
significantly (P<0.01 and P< 0.05, respectively)
inhibited fever induced by TPS. These data suggest that both
localised peripheral and brain IL-1 and TNF-[alpha] are involved
directly in the pyrogenic response to inflammation. The results
indicate that in the periphery IL-1 and TNF-[alpha] cause increased
production of IL-6, the most likely candidate as a circulating
endogenous pyrogen.
Received 29 May 1996; accepted in final form 2 October 1996.
APS Manuscript Number R300-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996