Cytokine production by bronchoalveolar lavage cells in chronic beryllium disease

Chronic beryllium disease (CBD) begins as a sensitizing cell-mediated immune response to beryllium antigen that progresses to granulomatous lung disease. Previous studies demonstrated the involvement of proinflammatory cytokines in the disease process, but the pattern and regulation of cytokine release is unknown. Using bronchoalveolar lavage (BAL) cells from CBD patients in short-term tissue culture, we evaluated cytokine protein levels by enzyme-linked immunosorbent assay and T-lymphocyte proliferation by tritiated thymidine incorporation. We observed the beryllium-stimulated release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) but not interleukin-4 (IL-4). Beryllium-stimulated IFN-gamma release was sustained to 168 hr in culture, whereas IL-2 concentrations returned to baseline after 24 hr. Neutralization of IL-2 decreased beryllium-stimulated T-lymphocyte proliferation, but the level of proliferation remained elevated in comparison to unstimulated BAL cells. These data suggest that T helper 1 (Th1) lymphocytes participate in the beryllium disease process; that IFN-gamma levels remain elevated after IL-2 levels return to baseline; and that IL-2 participates directly in beryllium-stimulated T-cell proliferation, but other T-lymphocyte mitogenic cytokines may be involved.