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Pathogenesis of silicosis: Current concepts and hypotheses

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Abstract

Silicosis is caused by the inhalation of crystalline silica (silicon dioxide, SiO2) in various forms. This review proposes that the cascade of inflammatory and fibrotic events involved in cell-mediated, and possibly humoral, immune responses also produces silicosis. The hypothesis rests on the central concept that interactions between silica and pulmonary macrophages are the pivotal events in the pathogenesis of silicosis. Resident and recruited pulmonary macrophages demonstrate intimate contact with silica from the moment of deposition, and throughout the time the particles remain in the lung. The silica probably exerts its effects on the macrophages that ingest it by altering their function while they are alive, rather than merely by disrupting them. The macrophage appears to be stimulated to secrete mediator substances, such as interleukin-1 (IL-1), which alter the function and behavior of other cells. Lymphocytes and macrophages appear in close proximity to one another in developing silicotic nodules, and increased proportions of lymphocytes are found in bronchoalveolar lavage specimens from animals and humans with silica dust exposure. Hypothetically, macrophages influence and activate lymphocytes, which then feed back to amplify the response by stimulating the same or other recruited macrophages. An expanded and activated population of lymphocytes under the influence of IL-1 in turn can secrete a variety of lymphokines which profoundly alter monocyte/macrophage function. The macrophage has been implicated as a major cause for the fibrosis that accompanies silicosis. The products of activated T-lymphocytes, particularly interferon-gamma (IF-g), are potent stimulators of secretion from macrophages of a fibroblast growth competence factor, macrophage-derived growth factor (MDGF). IL-1 may have an additional stimulatory effect on fibroblasts. Neutrophils and macrophages also may be important in silicosis because of their potent ability to cause lung tissue injury. Silicosis provides a model of chronic diffuse interstitial immunologic and fibrotic lung disease in which the cause is known, can be applied in defined doses, and tracked in the lung throughout the course of the disease. Further studies should provide better understanding of the mechanisms that goven pulmonary injury, inflammation, repair, and fibrosis.

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  1. Pulmonary Unit, Given C-317, College of Medicine, University of Vermont, 05405, Burlington, VT, USA

    Gerald S. Davis

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Davis, G.S. Pathogenesis of silicosis: Current concepts and hypotheses. Lung 164, 139–154 (1986). https://doi.org/10.1007/BF02713638

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