American Journal of Respiratory and Critical Care Medicine 1997-12-01

Beryllium-stimulated release of tumor necrosis factor-alpha, interleukin-6, and their soluble receptors in chronic beryllium disease.

S S Tinkle, L S Newman

Index: Am. J. Respir. Crit. Care Med. 156(6) , 1884-91, (1997)

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Abstract

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 lnterleukin-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.