Escherichia coli lipopolysaccharides produce serotype-specific hypothermic response in biotelemetered rats.
We investigated whether LPS-induced hypothermia develops in a serotype-specific manner in biotelemetered conscious rats. Two different Escherichia coli serotypes of LPSs were injected at a dose of 250 mug/kg ip. E. coli O55:B5 LPS elicited an initial hypothermia and subsequent fever, but E. coli O111:B4 LPS caused more potent monophasic hypothermia. Serum tumor necrosis factor (TNF)-alpha levels were dramatically elevated at the initial phase of the hypothermia induced by both LPSs. This elevation tended to subside at the nadir of E. coli O55:B5 LPS-induced response but progressively increased at the nadir of E. coli O111:B4 LPS hypothermia. Serum IL-10 levels were moderately elevated at the initial phase of the hypothermia and persisted at the same level at the nadir of each LPS-induced response. No change was observed at the serum IL-18 levels. A selective cyclooxygenase (COX)-1 enzyme inhibitor, valeryl salicylate (20 mg/kg sc), abolished the hypothermia without any effect on the elevated cytokine levels. Another COX-1-selective inhibitor, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560; 1 mg/kg sc) inhibited hypothermic responses as well. Meanwhile, cytokine levels were also reduced by SC-560 treatment. These findings suggest that LPS-induced hypothermia may have serotype-specific characteristics in rats. E. coli O111:B4 LPS has more potent hypothermic activity than E. coli O55:B5 LPS; that may presumably be related to its higher or sustained capability to release antipyretic cytokines, such as TNF-alpha. COX-1 enzyme may be involved in the generation of the hypothermia, regardless of the type of LPS administered.
Akarsu
Eyup S
ES
Ankara Univ, School of Medicine, Dept of Pharmacology and Clinical Pharmacology, Sihhiye, Ankara, Turkey. akarsu@dialup.ankara.edu.tr
Mamuk
Soner
S
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism*; D007035:Hypothermia / Q000139:chemically induced* / Q000188:drug therapy; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000633:toxicity*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology; D013686:Telemetry; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D020382:Interleukin-18; D008070:Lipopolysaccharides; D011720:Pyrazoles; C115461:SC 560; D012459:Salicylates; D014409:Tumor Necrosis Factor-alpha; C401835:valerylsalicylate; D016753:Interleukin-10