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-mu-g, 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-mu-g/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.