Interleukin-6 is a centrally acting endogenous pyrogen in the rat.
Intracerebroventricular (i.c.v.) injection of human recombinant interleukin-6 (IL-6; 20-100 ng) caused significant increases in colonic temperature and resting oxygen consumption (VO2) in conscious rats. These effects were prevented by pretreatment with a cyclooxygenase inhibitor (flurbiprofen, 1 mg/kg, i.p.) or a corticotrophin-releasing factor antagonist (alpha-helical CRF9-41, 25 micrograms, i.c.v.). Higher doses of IL-6 (i.c.v.) caused only small changes in VO2 and temperature, and very high doses given intravenously (i.v.) (4 micrograms/kg) were required to stimulate these parameters. Central injection of anti-rat IL-6 antibody inhibited the effects of interleukin-1 beta (i.c.v.) or endotoxin injection (i.p.) on colonic temperature and VO2 in conscious rats. These data indicate that IL-6 is an important endogenous pyrogen that acts within the central nervous system.
Rothwell
N J
NJ
Department of Physiology, University of Manchester, U.K.
Busbridge
N J
NJ
Lefeuvre
R A
RA
Hardwick
A J
AJ
Gauldie
J
J
Hopkins
S J
SJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005334:Fever / Q000139:chemically induced; D005480:Flurbiprofen / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011749:Pyrogens / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D015850:Interleukin-6; D011749:Pyrogens; D011994:Recombinant Proteins; D005480:Flurbiprofen