Partial IL-10 inhibition of the cell-mediated immune response in chronic beryllium disease

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 lym phocyte proliferation, thus contributing to the development of granulomatou s lung disease. To test this hypothesis, we used bronchoalveolar lavage cel ls from control and CBD subjects to evaluate the beryllium salt-specific pr oduction of endogenous IL-10 and the effects of exogenous human rIL-10 (rhI L-10) on HLA expression, on the production of IL-2, IFN-gamma, and TNF-alph a, and on T lymphocyte proliferation. Our data demonstrate that beryllium-s timulated bronchoalveolar lavage cells produce IL-10, and the neutralizatio n of endogenous IL-10 does not increase significantly cytokine production, HLA expression, or T lymphocyte proliferation. Second, the addition of exce ss exogenous rhIL-10 partially inhibited the beryllium-stimulated productio n of IL-2, IFN-gamma, and TNF-alpha; however, we measured no change in T ly mphocyte proliferation or in the percentage of alveolar macrophages express ing HLA-DP, Interestingly, beryllium salts interfered with an IL-10-stimula ted decrease in the percentage of alveolar macrophages expressing HLA-DR. W e conclude that, in the CBD-derived, beryllium-stimulated cell-mediated imm une response, low levels of endogenous IL-10 have no appreciable effect; ex ogenous rhIL-10 has a limited effect on cytokine production and no effect o n T lymphocyte proliferation or HLA expression.