Plasma profiles of IL-6 and TNF with fever-inducing doses of lipopolysaccharide in dogs.
This study was designed to test the tumor necrosis factor (TNF) WEHI 164 clone 13 bioassay and the interleukin 6 (IL-6) B9 bioassay for sensitivity to endogenously produced dog TNF and IL-6 and then to use these assays to examine the associations between these cytokines and lipopolysaccharide (LPS)-induced fever. When dogs were injected with LPS (40, 10, 1, 0.1, and 0.01 microgram/kg), the resulting fever was dose dependent. A plot of plasma cytokine changes over time following LPS injections showed that the plasma TNF-like activity appeared to increase in an all-or-none dose response, whereas the increase in plasma IL-6-like activity appeared to be log dose dependent. Plasma TNF-like and IL-6-like activity were then separately plotted against temperature change (fever). Statistical analysis supported the interpretation that both TNF-like and IL-6-like activity were related to LPS-fever in an all-or-none manner, with IL-6 having a threshold region. We conclude that if these cytokines are circulating mediators of fever, they may induce fever in an all-or-none fashion.
LeMay
D R
DR
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
LeMay
L G
LG
Kluger
M J
MJ
D'Alecy
L G
LG
D000818:Animals; D001685:Biological Factors / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D016207:Cytokines; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000097:blood* / Q000139:chemically induced / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D001685:Biological Factors; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha