NATURAL PORCINE SURFACTANT INHIBITS SUPEROXIDE ANIONS AND PROINFLAMMATORY MEDIATORS RELEASED BY STIMULATED HUMAN MONOCYTES. |[dagger]| 1491

Pulmonary surfactant (PS) may modulate inflammation in lungs. In lung injury, monocytes (MΘ) that accumulate within the lung become activated and participate in the inflammatory response. We, therefore, investigated the pro-inflammatory functions of stimulated human blood MΘ after an overnight preincubation with or without a modified natural porcine PS(Curosurf)(500-1000μg/ml). The target functions examined were: 1)the production of superoxide anions (O2) stimulated either with PMA (100 ng/ml, 30 min) or bacterial extract OM-85 (1 mg/ml, 30 min), preincubated with or without Staurosporine (SS) (1μM), an inhibitor of PKC, and measured by SOD inhibitable reduction of ferricytochrome C; 2)the release of LTC-4 stimulated with A28187 (10μM, 10 min) and measured by EIA; 3)the release of PGE2 and TxB2 stimulated with OM-85 (1 mg/ml. overnight) and measured by EIA; 4)the release of TNFα stimulated with OM-85 (1 mg/ml, overnight) and measured by ELISA. Between group comparisons by Kruskal-Wallis & Mann-Whitney test *p<0.05 vs. controls. The present study provides experimental evidence of an anti-inflammatory role of modified natural porcine PS in vitro. We propose that the mechanism involved is PKC-independent. If confirmed in vivo, such an anti-inflammatory property may explain, at least in part, the beneficial therapeutic effects of Curosurf in neonatal and adult RDS. Table