Tumor necrosis factor-alpha and fever after peripheral inflammation in the rat.
The involvement of endogenous tumor necrosis factor-alpha (TNF-alpha) in the pyrogenic [i.e., rise in colonic temperature (Tc)] and thermogenic [increase in oxygen consumption (VO2)] responses to inflammation was investigated in rats subjected to an intramuscular injection of turpentine. Turpentine administration caused a rise in Tc and VO2 within 2 h (0.9 +/- 0.1 degrees C, 27 +/- 2%, respectively). Eighteen to twenty hours after turpentine, the magnitude of these responses had increased (2.3 degrees C fever and a 28% increase in metabolic rate compared with control animals) and was associated with marked inflammation in the injected limb. A rapid (by 4 h) and sustained rise in the plasma concentration of the endogenous pyrogen IL-6, but not TNF-alpha, was also observed. Intravenous pretreatment with a TNF-alpha antiserum attenuated the rise in Tc observed 2, 8, and 18 h after turpentine injection and almost abolished the hypermetabolic response observed at 18 h. In addition, the TNF-alpha antiserum inhibited the peak rise (8 h) in plasma IL-6 by 76%. These findings indicate that endogenous TNF-alpha is involved in fever and hypermetabolism during inflammation and that it may exert these effects by inducing the release of IL-6 into circulation.
Cooper
A L
AL
University of Manchester, United Kingdom.
Brouwer
S
S
Turnbull
A V
AV
Luheshi
G N
GN
Hopkins
S J
SJ
Kunkel
S L
SL
Rothwell
N J
NJ
D000818:Animals; D001831:Body Temperature; D003106:Colon; D005334:Fever / Q000503:physiopathology*; D007106:Immune Sera / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D007700:Kinetics; D008297:Male; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*; D014425:Turpentine
D007106:Immune Sera; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014425:Turpentine