PAF modulates eicosanoids and TNF release in immune-complex arthritis in rats.
The participation of lipid mediators and tumor necrosis factor (TNF) on an experimental model of immune-complex arthritis was investigated. Male Wistar rats received intraarticular injection of rabbit antibodies to bovine serum albumin into the knee joint followed by i.v. injection of the antigen. The levels of eicosanoids and TNF released into the synovial exudates were then assessed using ELISA and the L929 lytic cell assay, respectively. Increase in the levels of LTB4, TXB2 and PGE2 were detected 5 min, 5 min, and 6 h after arthritis induction, respectively. Pretreatment with the PAF receptor antagonist WEB 2170 decreased the levels of PGE2 and increased those of LTB4, without altering TXB2 levels. Increase in the levels of TNF was detected at 3 h of arthritis. Pretreatment with either the cycloxygenase inhibitor indomethacin or the 5-lipoxygenase inhibitor L-663,536 had no effect on TNF levels. Pretreatment with WEB 2170 significantly decreased TNF levels. These results are the first demonstration of eicosanoids and TNF release in immune-complex arthritis. The data also suggest that PAF had both a positive and negative modulatory role on the release of PGE2 and LTB4, respectively. Moreover, TNF release into the synovial exudate did not depend on eicosanoids whereas platelet activating factor (PAF) appeared to mediate the release of this cytokine in the model.
Rocha
F A
FA
Faculdade de Medicina, Universidade Federal de Ceará, Brazil.
Andrade
L E
LE
Russo
M
M
Jancar
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism*; D001183:Arthus Reaction / Q000378:metabolism*; D002417:Cattle; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007270:Injections, Intra-Articular; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013582:Synovial Fluid / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D002722:Chlorobenzenes
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015232:Dinoprostone; D015777:Eicosanoids; D007211:Indoles; D007213:Indomethacin; D007975:Leukotriene B4; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D013929:Thromboxane B2; D014409:Tumor Necrosis Factor-alpha; C060893:MK-886; D002722:Chlorobenzenes