Anti-inflammatory action of interleukin 1 through the pituitary-adrenal axis in rats.
The influence of lipopolysaccharide (LPS) and the endogenous pyrogens, recombinant human interleukin 1 (rHu-IL 1) and tumor necrosis factor (rHu-TNF), on acute inflammation was investigated in rats. LPS (0.3-3 micrograms/kg i.v.), rHu-IL 1 alpha (3-30 micrograms/kg), rHu-IL 1 beta (0.3-3 micrograms/kg) and rHu-TNF (3-30 micrograms/kg) inhibited the hind paw edema induced by carrageenan in a dose-related manner. The potency of rHu-IL 1 beta was 10 times or more than of rHu-IL 1 alpha. rHu-IL 1 alpha and rHu-TNF also inhibited the dextran-induced hind paw edema. Both types of rHu-IL 1 (0.001-10 ng/paw) neither inhibited nor enhanced the edema when given directly into the inflamed paw. rHu-IL 1 alpha did not show any significant anti-edema activity in adrenalectomized rats. The 3 cytokines tested caused a significant increase in the plasma levels of ACTH and corticosterone after i.v. administration; the potency of rHu-IL 1 beta was about 10 times that of rHu-IL 1 alpha. These results suggest that both rHu-IL 1 and rHu-TNF inhibit paw edema at least in part through pituitary-adrenal axis stimulation, and that rHu-IL 1 has no pro-inflammatory action in the paw edema induced by carrageenan in rats.
Nakamura
H
H
Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Motoyoshi
S
S
Kadokawa
T
T
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents; D003345:Corticosterone / Q000378:metabolism; D003911:Dextrans / Q000494:pharmacology; D004487:Edema / Q000473:pathology; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D003911:Dextrans; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone