CHARACTERIZATION OF EXOSURF (SURFACTANT)-MEDIATED SUPPRESSION OF STIMULATED HUMAN ALVEOLAR MACROPHAGE CYTOKINE RESPONSES

Previous studies in our laboratory demonstrated that the synthetic sur factant Exosurf (Burroughs Wellcome Co.) inhibited endotoxin-stimulate d cytokine secretion from human alveolar macrophages in vitro. The pur pose of the present study was to further characterize the suppressive effects of Exosurf, which consists of dipalmitoylphosphatidylcholine ( DPPC), cetyl alcohol (spreading agent), and tyloxapol (nonionic disper sing agent). Suppression was not stimulus specific in that Exosurf als o significantly reduced cytokine production elicited by either Staphyl ococcus aureus or recombinant interleukin-1. Suppression was also medi ated by a modified bovine surfactant (Survanta), which, in contrast to Exosurf, contains the surfactant-associated proteins B and C, and sev eral different phospholipids, but no cetyl alcohol or, tyloxapol. This suggests that suppression of macrophage cytokines is not specific to Exosurf. Both cell associated and secreted tumor necrosis factor and i nterleukin-l were reduced by Exosurf, indicating that Exosurf is not s imply blocking cytokine release. At 3 h, cytokine mRNA levels were not different between Exosurf-treated and untreated cells. However, at 8 and 24 h, cytokine mRNA levels were lower in Exosurf-treated cells. Th e observations that mRNA levels were decreased at 8 and 24 h and that cellular cytokine release was not blocked suggest that Exosurf's effec t may in part be pretranslationally mediated. Collectively, these data add to previous work indicating that pulmonary surfactant may play a critical role in reducing inflammatory cytokine production associated with the adult respiratory distress syndrome and similar disorders.