The relationship between alveolar macrophage TNF, IL-1, and PGE2 release, alveolitis, and disease severity in...

A mononuclear cell alveolitis, comprised in part of activated macrophages, is thought to precede granuloma formation and fibrosis in pulmonary sarcoidosis. Tumor necrosis factor-alpha (TNF), interleukin 1-beta (IL-1), and prostaglandin E2 (PGE2) are potent mediators released by activated alveolar macrophages. To determine if alveolar macrophage TNF, IL-1, and PGE2 release was associated with clinically progressive pulmonary sarcoidosis, we obtained alveolar macrophages from bronchoalveolar lavage of 68 patients with biopsy specimen-confirmed sarcoidosis, cultured the macrophages in the presence and absence of lipopolysaccharide (10 mg/L) for 24 h, and measured TNF (enzyme-linked immunosorbent assay), IL-1 (enzyme-linked immunosorbent assay), and PGE2 (radioimmunoassay) release. Alveolar macrophages from most patients with sarcoidosis spontaneously released TNF, IL-1, and PGE2. The amounts of these mediators released (either spontaneously or following lipopolysaccharide stimulation) did not positively correlate with the numbers of any of the cells in bronchoalveolar lavage fluid, the clinical status of disease (stable vs deterioration), steroid usage, or cigarette smoking. The relative release of each of the individual mediators, however, was highly correlated with the release of the other mediators. The studies suggest that these markers of alveolar macrophage activation from a single bronchoalveolar lavage are poor indicators of clinically progressive disease.