CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT IS NECESSARY FOR INTERLEUKIN-1-INDUCED LUNG LEAK IN RATS

Because interleukin-1 (IL-1) is not a potent chemoattractant intrinsic ally, our goal was to determine whether cytokine-induced neutrophil ch emoattractant (CINC) mediates neutrophil accumulation and leak that oc cur in lungs of rats given IL-1 intratracheally. We found that rats gi ven IL-1 intratracheally had increased lung lavage CINC concentrations , lung myeloperoxidase (MPG) activity, lung lavage neutrophil numbers, and lung leak compared with saline-treated control rats. In parallel, rats given increasing doses of anti-CINC antibody along with IL-1 int ratracheally had progressively decreased lung lavage CINC concentratio ns, lung lavage neutrophil numbers, and lung leak, but the same lung M PO activity, as did rats given only IL-1 intratracheally. In addition, lavage CINC concentrations correlated with lavage neutrophil numbers in rats. Because CINC is a chemoattractant in vitro and because anti-C INC antibody decreased lung leak induced by IL-1, CINC was then given alone intratracheally. Rats given only CINC intratracheally had the sa me lung MPO activity, lung lavage neutrophil numbers, and lung leak as did saline-treated control rats. These observations suggest that inst illing IL-1 intratracheally induces lung leak via a CINC-dependent pat hway but that administering CINC alone in concentrations exceeding the levels measured in lung lavages from IL-1-treated rats is not suffici ent to cause lung neutrophil accumulation and lung leak.