MEPACRINE DECREASES LUNG LEAK IN RATS GIVEN INTERLEUKIN-1 INTRATRACHEALLY

We hypothesized that phospholipase A(2) (PLA(2)) metabolites contribut e to the acute, neutrophil-dependent, edematous lung leak that develop s after administration of interleukin-1 (IL-1) intratracheally to rats and tested this premise by using mepacrine to inhibit PLA(2) activity in vivo. We found that lung PLA(2) activity, lung lavage phospholipid content, lung leak index, lung weight gain, and lung lavage protein c oncentrations were increased in rats given IL-1 intratracheally compar ed with sham-treated control rats. By comparison, lungs of mecaprine a nd IL-1-treated rats had decreased PLA(2) activity, lavage phospholipi d content, leak, weight gain, and lavage protein increases compared wi th rats given IL-1 intratracheally. Mepacrine treatment also decreased lung neutrophil accumulation, but not lung lavage cytokine-induced ne utrophil chemoattractant (CINC) levels, in rats given IL-1 intratrache ally. In parallel experiments, mepacrine treatment reduced the adhesio n of human neutrophils to IL-1-treated human umbilical vein endothelia l cells in vitro. Our results indicate that PLA(2) activity participat es in the lung neutrophil retention and pulmonary vascular leak that d evelops in rats given IL-1 intratracheally.