Tumour necrosis factor-alpha mediates neutrophil migration to the knee synovial cavity during immune inflammation.
Tumour necrosis factor (TNF)-alpha, interleukin-1beta, interleukin-8 and leukotriene B4 have an important role on neutrophil recruitment during immune-inflammation. Here we evaluated the participation of several inflammatory mediators on ovalbumin-induced neutrophil recruitment in the knee articular space of immunized rats. Ovalbumin administration in immunized, but not in control, rats induced a dose- and time-dependent neutrophil accumulation, which was inhibited by dexamethasone, pentoxifylline or thalidomide, but not by selective inhibitors of nitric oxide (nitro-L-arginine), platelet-activating factor (BN50730 or UK74505), prostaglandins (indomethacin), histamine (meclisine) or leukotriene B4 (MK 886 and CP105,696). Anti-TNF-alpha antiserum, but not anti-interleukin-1beta or anti-CINC-1 (cytokine-induced neutrophil chemoattractant 1) antisera, impaired ovalbumin-induced neutrophil accumulation. High amounts of TNF-alpha were detected in the exudates, which was inhibited by dexamethasone, pentoxifylline and thalidomide. These results suggest a specific role for TNF-alpha in this model, and the ability of pentoxifylline and thalidomide to inhibit both neutrophil influx and TNF-alpha release may have therapeutic implications in arthritis.
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Gustavo
G
Bombini
Cláudio
C
Canetti
Francisco A C
FA
Rocha
Fernando Q
FQ
Cunha
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D007719:Knee Joint / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013582:Synovial Fluid / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*
D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin