ANTIINFLAMMATORY ACTIVITY OF TISSUE-PLASMINOGEN ACTIVATOR IN THE CARRAGEENAN RAT FOOTPAD MODEL

Exogenous plasminogen activators (PAs), such as streptokinase (SK) and tissue plasminogen activator (tPA), have been shown to significantly improve the mortality of patients with acute myocardial infarction. Ho wever, reperfusion of the myocardium is associated with neutrophil act ivation and infiltration into the infarct region. Plasminogen activato rs influence neutrophil function in vitro, but no data exists regardin g the effect of exogenous PAs on inflammation in vivo. Therefore, we e valuated the effect of PAs on inflammation using the carrageenan-induc ed rat footpad inflammation model. The magnitude of carrageenan-induce d inflammation was determined by water-displacement and neutrophil inf iltration, following administration of either tPA or SK to Sprague-Daw ley rats. tPA (12 mg/kg) inhibited carrageenan-induced inflammation (p < .01). In contrast, administration of SK (40,000 U/kg) enhanced infl ammation. These results suggest that exogenous PAs influence the infla mmatory process but specific PAs differ in their actions. Ultimately, these differences may influence the efficacy of these agents in the ma nagement of acute myocardial infarction and lead to further evaluation of tPA in other inflammatory diseases such as acute respiratory distr ess syndrome (ARDS) and rheumatoid arthritis (RA), in which neutrophil -mediated injury is likely. Copyright 1997 Elsevier Science Inc.