REGULATION OF HUMAN ALVEOLAR MACROPHAGE INFLAMMATORY CYTOKINES BY TYLOXAPOL - A COMPONENT OF THE SYNTHETIC SURFACTANT EXOSURF

We previously demonstrated that the synthetic surfactant Exosurf and a modified natural surfactant, Survanta, both down-regulated endotoxin- stimulated production of inflammatory cytokines (tumor necrosis factor -alpha, interleukin-1 beta, interleukin-6) in human alveolar macrophag es. To further characterize the source of the inhibitory effect of sur factant, the three individual components of Exosurf were evaluated. Di palmitoylphosphatidylcholine had no effect on endotoxin-stimulated cyt okine secretion. Cetyl alcohol (spreading agent) compromised macrophag e function as measured by adherence. However, at concentrations equiva lent to those found in the complete surfactant (Exosurf) preparation, tyloxapol (nonionic dispersing agent) was inhibitory in a dose-depende nt manner. The viability of alveolar macrophages as assessed by 3-(4,5 -dimethylthiazol-2-yl)-2,5-dipheny tetrazolium bromide cleavage assay was not affected by incubation in Exosurf or any of its individual com ponents. Cytokine secretion and mRNA levels of endotoxin-stimulated al veolar macrophages were decreased by tyloxapol. These data suggest tha t tyloxapol alone, like Exosurf, has an inhibitory effect on cytokine production which may be pretranslationally mediated. (C) 1995 Academic Press, Inc.