Surfactant down-regulates synthesis of dna and inflammatory mediators in normal human lung fibroblasts. Thomassen, Mary Jane, Joyce M. Antal, Barbara P. Barna, Lisa T. Divis, David P. Meeker, and Herbert P. Wiedemann. Departments of Pulmonary and Critical Care Medicine and Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195-5038
APStracts 2:0162L, 1995.
The initial inflammatory event in the Adult Respiratory Distress Syndrome (ARDS) is followed by fibroproliferation and a cascade of fibroblast-derived mediators. Because lung fibroblasts may be exposed to surfactant as well as inflammatory cytokines during ARDS, we hypothesized that surfactant might modulate fibroblast activity. We previously demonstrated that surfactant inhibited production of inflammatory cytokines from endotoxin-stimulated human alveolar macrophages. In the current study the effects of surfactant on normal human lung fibroblast proliferative capacity and mediator production were examined. Both synthetic (Exosurf) and natural (Survanta) surfactant inhibited fibroblast 3H-thymidine incorporation. Examination of pre-S-phase events indicated stimulation of the immediate response gene, c-fos, and no effect on the G1/S cyclin, cyclin D 1, suggesting that the surfactant block occurred elsewhere prior to S phase. The antioxidant N-acetyl cysteine (NAC), like surfactant, inhibited 3H-thymidine incorporation. Furthermore, menadione, a generator of intracellular H2O2, stimulated fibroblast 3H-thymidine incorporation and this was inhibited by surfactant. Interleukin-1(IL-1) stimulated secretion of the inflammatory mediators, IL-6 and prostaglandin E2 (PGE2) was also inhibited by surfactant. These data suggest that surfactant may modify lung fibroblast participation in ARDS sequelae by down-regulating DNA synthesis and secondary inflammatory mediator production. 

Received 19 May 1995; accepted in final form 15 August 1995.
APS Manuscript Number L157-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.