Tumour necrosis factor production in a rat airpouch model of inflammation: role of eicosanoids.
TNF is a potent cytokine which can induce many of the pathological changes associated with inflammatory disease. In vitro studies have demonstrated that 5-lipoxygenase products promote the production of TNF by activated macrophages, suggesting that 5-lipoxygenase inhibitors may have therapeutic utility for the treatment of inflammatory conditions. A rat airpouch model of inflammation has been used to investigate the relationship between eicosanoid generation and TNF production in vivo. Injection of zymosan into the airpouch caused a time-dependent stimulation of TNF production which preceded leukotriene generation by at least 30 minutes. Injection of LPS into the airpouch also stimulated TNF production but not leukotriene generation. The selective 5-lipoxygenase inhibitors, ICI207968, A64077 and BWA4C, and the 5-lipoxygenase translocation inhibitor MK886, decreased leukotriene generation but enhanced TNF production. Taken together, these results do not support a role for 5-lipoxygenase products in the regulation of TNF production in vivo.
Ferrándiz
M L
ML
ICI Pharmaceuticals, Bioscience 1, Macclesfield, Cheshire, UK.
Foster
S J
SJ
D000818:Animals; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007700:Kinetics; D007975:Leukotriene B4 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015054:Zymosan
D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D015054:Zymosan; D015232:Dinoprostone; D007213:Indomethacin