Pulmonary sarcoidosis: patterns of cytokine release in vitro

This study was designed to investigate the ability of bronchoalveolar and blood mononuclear cells to produce inflammatory mediators in vitro in pulmonary sarcoidosis. Seventeen patients with pulmonary sarcoidosis (stage I n = 8; stage II/III n = 9) and 10 normal controls were investigated. Bronchoalveolar and peripheral blood mononuclear cells were cultured in serum-free medium, without stimulant, for 24 h, and the supernatants analysed for concentrations of interleukin (IL)-1 beta (IL-1 beta), IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma) and neopterin. Bronchoalveolar lavage cells (BALC) of sarcoid patients released significantly higher amounts of TNF-alpha, IL-6, IFN-gamma and neopterin in comparison to normal controls. When smokers were excluded, there was also an increased release of IL-1 beta and GM-CSF. In the sarcoid group, the levels of IL-1 beta, IL-6, TNF-alpha and GM-CSF showed highly significant correlations between each other, but not with IL-2, IFN-gamma or neopterin. Sarcoid patients whose BALC released more TNF-alpha or GM-CSF had higher percentage counts of alveolar macrophages but fewer lavage lymphocytes. In sarcoid patients, peripheral blood mononuclear cells (PBMNC) also released higher amounts of IL-1 beta, TNF-alpha, IL-6 and GM-CSF but less neopterin than normal controls. Patients whose PBMNC produced more IL-1 beta, IL-6 and GM-CSF had higher absolute and relative lavage neutrophil counts. No relationships were observed between cytokine release and radiographic or physiological markers of disease severity. We conclude from this study that sarcoid inflammation is associated with an increased and concerted release of monocyte/macrophage-derived cytokines not only in the lung but also in the peripheral blood. We speculate that the lymphokines, IFN-gamma and IL-2, are not the primary triggers.

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