Effect of GM-CSF on TNF-alpha and IL-1-beta production by alveolar macrophages and peripheral blood monocytes from patients with sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder of unknown origin characterized by activated T-lymphocytes and macrophages. Macrophage/monocyte-derived cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to be involved in the pathogenesis of sarcoidosis. Although the production of TNF-alpha and IL-1 by alveolar macrophages (AM) and peripheral monocytes (PM) in response to lipopolysaccharide (LPS) in sarcoidosis has been well demonstrated, the production of these cytokines in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) has not been delineated. The present studies were designed to examine the regulatory effect of GM-CSF on TNF-alpha and IL-1 beta production by AM and PM from patients with pulmonary sarcoidosis. Amounts of TNF-alpha and IL-1 beta in the culture supernatants of unstimulated AM from patients with sarcoidosis were significantly higher than those from normal subjects, whereas, there was no difference in the amounts of TNF-alpha and IL-1 beta in the culture supernatants of PM between patients with sarcoidosis and normal subjects. The amounts of TNF-alpha and IL-1 beta in the culture supernatants of GM-CSF or LPS-stimulated AM and PM were significantly higher than those of similarly stimulated AM and PM from normal subjects. This hyperresponsiveness of AM and PM to GM-CSF in patients with sarcoidosis might be relevant to the pathogenesis of sarcoidosis.