EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA GENE IN ALVEOLAR MACROPHAGES FROM PATIENTS WITH THE ADULT-RESPIRATORY-DISTRESS-SYNDROME

The adult respiratory distress syndrome (ARDS) is a complex syndrome in which pathogenesis is multifactorial. TNF-alpha, known to be pivotal in tissue damage, has been shown to have high levels in blood and alveolar fluid in ARDS. The identification of the cells responsible for this production in the alveolar milieu has not yet been reported. In order to evaluate the TNF-alpha gene expression in ARDS we have analyzed by in situ hybridization, using RNA probes, alveolar macrophages (AM) obtained by BAL from seven patients with ARDS, eight patients with miscellaneous respiratory diseases, and three control patients. In freshly collected AM from patients with ARDS, 66 +/- 14.5% cells expressed the TNF-alpha gene without in vitro stimulation. This TNF-alpha expression does not result from the BAL procedure itself since only a few unstimulated control AM contained TNF-alpha mRNA transcripts. TNF-alpha expression in AM is not restricted to patients with ARDS since it has also been observed in miscellaneous respiratory diseases; however, this expression is a constant feature in ARDS. These results demonstrated the major role of AM in the intra-alveolar production of TNF-alpha, and they point out the necessity in ARDS for a specific intra-alveolar therapy.