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Am. J. Respir. Crit. Care Med., Volume 156, Number 6, December 1997, 1884-1891

Beryllium-stimulated Release of Tumor Necrosis Factor-alpha , Interleukin-6, and Their Soluble Receptors in Chronic Beryllium Disease

SALLY S. TINKLE and LEE S. NEWMAN

National Jewish Medical and Research Center, Division of Environmental and Occupational Health Sciences, National Jewish Center for Immunology and Respiratory Medicine; and Division of Pulmonary Sciences and Critical Care Medicine, Departments of Medicine and Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado

Chronic beryllium disease (CBD) provides a model system in which to evaluate the antigen-stimulated, cell-mediated, immune response that leads to granulomatous lung disease. We hypothesized that beryllium salts would stimulate bronchoalveolar lavage (BAL) cell release of tumor necrosis factor-alpha (TNF-alpha ) and interleukin-6 (IL-6), and their soluble receptors, soluble TNF receptor I (sTNF RI), sTNF RII, and sIL-6R and that chronic exposure to antigen would increase production of soluble receptors in the serum and BAL fluid (BALF) of beryllium-sensitized and CBD patients. We have demonstrated (1) similar constitutive TNF-alpha , IL-6, and soluble receptor production by control subjects and CBD patients, (2) a BeSO4-stimulated increase in TNF-alpha and IL-6 production by CBD-derived BAL cells, and (3) a BeSO4-induced decrease in sTNF RII production by BAL cells from control subjects. We measured increased serum sTNF RI and serum and BALF sIL-6R in beryllium-sensitized subjects and increased sTNF RI and RII in serum and sIL-6R and sTNF RII and BALF in CBD patients. These changes correlated with pulmonary lymphocytosis and clinical measures of disease severity, indicating that soluble receptors may reflect disease status.




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