BERYLLIUM-STIMULATED RELEASE OF TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-6, AND THEIR SOLUBLE RECEPTORS IN CHRONIC BERYLLIUM DISEASE

Chronic beryllium disease (CBD) provides a model system in which to ev aluate the antigen-stimulated, cell-mediated, immune response that lea ds to granulomatous lung disease. We hypothesized that beryllium salts would stimulate bronchoalveolar lavage (BAL) cell release of tumor ne crosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and their so luble receptors, soluble TNF receptor I (sTNF RI), sTNF RII, and sIL-6 R and that chronic exposure to antigen would increase production of so luble receptors in the serum and BAL fluid (BALF) of beryllium-sensiti zed and CBD patients. We have demonstrated (1) similar constitutive TN F-alpha, IL-6, and soluble receptor production by control subjects and CBD patients, (2) a BeSO4-stimulated increase in TNF-alpha and IL-6 p roduction by CBD-derived BAL cells, and (3) a BeSO4-induced decrease i n sTNF RII production by BAL cells from control subjects. We measured increased serum sTNF RI and serum and BALF slL-6R in beryllium-sensiti zed subjects and increased sTNF RI and RII in serum and sIL-6R and sTN F RII and BALF in CBD patients. These changes correlated with pulmonar y lymphocytosis and clinical measures of disease severity, indicating that soluble receptors may reflect disease status.