Contribution of TNFalpha, IL-1beta and CINC-1 for articular incapacitation, edema and cell migration in a model of LPS-induced reactive arthritis.
The protective effect of anti-CINC-1, -TNFalpha and -IL-1beta antisera on articular inflammatory incapacitation, articular diameter and synovial fluid cell content, which are correlated to nociception, edema and cell migration, respectively, were evaluated in a rat model of LPS-induced reactive arthritis. In this model, Escherichia coli lipopolysaccharide (LPS; 30 ng) was injected in a knee-joint previously primed with carrageenan (300 microg). Articular incapacitation was evaluated hourly by the automated registering of the knee-joint function during animal walking, and the knee-joint edema was evaluated by measuring the articular diameter increase. After 6 h, the animals were euthanized for collecting synovial fluid for the evaluation of cell migration. LPS produced dose-dependent incapacitation and edema. Anti-TNFalpha, -IL-1beta, and -CINC-1 antisera (20 and 40 microl) were used as pretreatment into knee-joint before LPS injection. At higher dose, Anti-TNFalpha and anti-CINC-1 were able to inhibit incapacitation, articular edema and mononuclear (MON) migration. Anti-IL1beta did not affect incapacitation at any dose, although inhibited edema and cell migration. Surprisingly, the higher dose of anti-IL1beta antisera did not inhibit cell migration, although inhibited articular edema. These findings corroborate the role TNFalpha has in different forms of arthritis, but points out the idea that CINC-1 (the homologue for human IL-8) may constitute a promising target for reactive arthritis management. Indeed, the potent antiedematogenic effect, and principally the anti-migration effect of anti-CINC-1, raises the possibility of a better control of disease progression than with anti-IL-1beta therapies.
Bressan
Elisângela
E
Department of Pharmacology, CCB, Federal University of Santa Catarina, Campus Trindade, Florianópolis, SC 88040-900, Brazil.
Cunha
Fernando De Queiroz
Fde Q
Tonussi
Carlos Rogério
CR
D000818:Animals; D000906:Antibodies / Q000276:immunology; D016918:Arthritis, Reactive / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000378:metabolism*; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism*; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013582:Synovial Fluid; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha