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Partial IL-10 inhibition of the cell-mediated immune response in chronic beryllium disease.
Tinkle SS; Kittle LA; Newman LS
J Immunol 1999 Sep; 163(5):2747-2753
Chronic beryllium disease (CBD) provides a human disorder in which to study the delayed type IV hypersensitivity response to persistent Ag that leads to noncaseating pulmonary granuloma formation. We hypothesized that, in CBD, failure of IL-10 to modulate the beryllium-specific, cell-mediated immune response would result in persistent, maximal cytokine production and T lymphocyte proliferation, thus contributing to the development of granulomatous lung disease. To test this hypothesis, we used bronchoalveolar lavage cells from control and CBD subjects to evaluate the beryllium salt-specific production of endogenous IL-10 and the effects of exogenous human rIL-10 (rhIL-10) on HLA expression, on the production of IL-2, IFN-gamma, and TNF-alpha, and on T lymphocyte proliferation. Our data demonstrate that beryllium-stimulated bronchoalveolar lavage cells produce IL-10, and the neutralization of endogenous IL-10 does not increase significantly cytokine production, HLA expression, or T lymphocyte proliferation. Second, the addition of excess exogenous rhIL-10 partially inhibited the beryllium-stimulated production of IL-2, IFN-gamma, and TNF-alpha; however, we measured no change in T lymphocyte proliferation or in the percentage of alveolar macrophages expressing HLA-DP. Interestingly, beryllium salts interfered with an IL-10-stimulated decrease in the percentage of alveolar macrophages expressing HLA-DR. We conclude that, in the CBD-derived, beryllium-stimulated cell-mediated immune response, low levels of endogenous IL-10 have no appreciable effect; exogenous rhIL-10 has a limited effect on cytokine production and no effect on T lymphocyte proliferation or HLA expression.
Immune-reaction; Beryllium-disease; Hypersensitivity; Immune-system-disorders; Pulmonary-system-disorders; Respiratory-system-disorders; Lung-disease
Dr. Sally S. Tinkle, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
Issue of Publication
The Journal of Immunology
Page last reviewed: September 11, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division