Kinetics of systemic and intrahypothalamic IL-6 and tumor necrosis factor during endotoxin fever in guinea pigs.
The time course of activity of interleukin-6 (IL-6) and tumor necrosis factor (TNF) was measured in blood plasma and hypothalamic push-pull perfusates during the febrile response to intramuscular injection of bacterial endotoxin (Escherichia coli, 20 micrograms/kg) in 24 guinea pigs. Injection of endotoxin caused a dramatic increase of IL-6 activity in plasma. The logarithmic values of plasma IL-6 activities showed a linear correlation to the febrile change in body temperature (r = 0.898) during the whole time course of fever. IL-6 activity in hypothalamic perfusates increased 12-fold in the first hour after pyrogen application and declined slowly despite the further increase in body temperature. Hypothalamic IL-6 activity did not correlate with the febrile increase in body temperature (r = -0.048). TNF activity in plasma, not detectable before pyrogen application, had its peak in the first hour after endotoxin injection and rapidly declined to 15-20% of the peak activity within the next 2 h and to an undetectable value 5 h after injection. In the hypothalamus TNF was not detectable before endotoxin injection, but it could be monitored in most animals after pyrogen application without a clear correlation to the fever response. These results taken together indicate that endotoxin fever represents a physiological situation in which production and release of cytokines in the peripheral immune system and in the hypothalamus are regulated and stimulated in independent patterns.
Roth
J
J
Physiologisches Institut, Klinikum der Justus-Liebig-Universität, Giessen, Germany.
Conn
C A
CA
Kluger
M J
MJ
Zeisberger
E
E
D000818:Animals; D001831:Body Temperature; D004731:Endotoxins / Q000097:blood; D005334:Fever / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D006168:Guinea Pigs; D007032:Hypothalamus, Anterior / Q000378:metabolism*; D007273:Injections, Intramuscular; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha