title: Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages.
abstract: Tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) are inflammatory cytokines produced by alveolar macrophages (AMs) and implicated in sepsis-related adult respiratory distress syndrome (ARDS). Preliminary findings from clinical trials suggest that aerosolized delivery of the synthetic surfactant Exosurf (Burroughs Wellcome Co.) reduces mortality in patients with sepsis-induced ARDS. The purpose of the present study was to examine the effect of Exosurf on inflammatory cytokine secretion from AMs in vitro. AMs were obtained from normal nonsmoking adult volunteers. Secreted TNF, IL-1, IL-6, and IL-8 were measured by enzyme-linked immunoassays in 24 h culture fluids of AMs. Exosurf inhibited LPS-stimulated TNF, IL-1, and IL-6 secretion in a dose-dependent fashion. IL-8 secretion was not affected by Exosurf under these conditions. However, if AMs were preincubated for 24 h in media and then LPS-stimulated, IL-8 secretion was inhibited by Exosurf. Regulation of IL-8 production may differ from TNF, IL-1, and IL-6. Unstimulated cytokine secretion was not affected by any of the tested concentrations of Exosurf. The inhibitory effect of Exosurf on endotoxin-induced cytokine secretion by human AMs suggests that Exosurf may modulate inflammatory cytokine production in the lung.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, OH 44195-5038.
authors.forename: M J
authors.initials: MJ
authors.lastname: Thomassen
authors.forename: D P
authors.initials: DP
authors.lastname: Meeker
authors.forename: J M
authors.initials: JM
authors.lastname: Antal
authors.forename: M J
authors.initials: MJ
authors.lastname: Connors
authors.forename: H P
authors.initials: HP
authors.lastname: Wiedemann
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D004338:Drug Combinations; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D005233:Fatty Alcohols / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology; D011663:Pulmonary Surfactants / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D004731:Endotoxins; D005233:Fatty Alcohols; D011663:Pulmonary Surfactants; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination