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 macrophages. To further characterize the source of the inhibitory effect of surfactant, the three individual components of Exosurf were evaluated. Dipalmitoylphosphatidylcholine had no effect on endotoxin-stimulated cytokine secretion. Cetyl alcohol (spreading agent) compromised macrophage function as measured by adherence. However, at concentrations equivalent to those found in the complete surfactant (Exosurf) preparation, tyloxapol (nonionic dispersing agent) was inhibitory in a dose-dependent manner. The viability of alveolar macrophages as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide cleavage assay was not affected by incubation in Exosurf or any of its individual components. Cytokine secretion and mRNA levels of endotoxin-stimulated alveolar macrophages were decreased by tyloxapol. These data suggest that tyloxapol alone, like Exosurf, has an inhibitory effect on cytokine production which may be pretranslationally mediated.
Thomassen
M J
MJ
Department of Pulmonary, Cleveland Clinic Foundation, Ohio 44195-5038, USA.
Antal
J M
JM
Divis
L T
LT
Wiedemann
H P
HP
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000494:pharmacology; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013501:Surface-Active Agents / Q000494:pharmacology*
D016207:Cytokines; D004338:Drug Combinations; D005233:Fatty Alcohols; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D013501:Surface-Active Agents; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; C016811:tyloxapol