The modulatory role played by TNF-alpha and IL-1 beta in the inflammatory responses induced by carrageenan in the mouse model of pleurisy

We describe here the modulation caused by intrapleural (i.pl.) injection of the cytokines TNF-alpha and IL-1 beta and their specific antibodies in the early (4 h) and late (48 h) inflammatory responses caused by injection of carrageenan (Cg) into the mouse pleural cavity. The antibodies against TNF- alpha and IL-1 beta, when injected 30 min prior to Cg, reduced, in a graded and significant manner, both exudation and cell migration in the early (4 h) phase, while they potentiated or had no effect in the late (48 h) phase of Cg response. The natural IL-1 receptor antagonist IL-1RA, given 30 min p rior to Cg, reduced the exudation by about 50% and abolished the total and differential cell migration in the early (4 h) and late (48 h) phases of th e Cg responses. The i.pl. injection of TNF-alpha or IL-1 beta, 5 min prior to Cg, caused graded increase in the exudation of the early (4 h) and late (48 h) phases of the Cg-induced inflammatory responses. In contrast, these treatments markedly reduced the total and differential cell migration at 4 h, while having little or no effect on the late (48 h) phase of the Cg pleu risy. These findings extend previous results and demonstrate that the pro-i nflammatory cytokines TNF-alpha and IL-1 beta have a critical role in contr olling both cell migration and exudation caused by injection of Cg in the m ouse pleural cavity. Together, these findings may be relevant to the unders tanding of the mechanisms involved in airway inflammatory responses. (C) 20 01 Academic Press.