INCREASED SPONTANEOUS INTERLEUKIN-10 RELEASE FROM ALVEOLAR MACROPHAGES IN ACTIVE PULMONARY SARCOIDOSIS

Abstract

The study was designed to determine whether alveolar macrophages (AM) in acute pulmonary sarcoidosis release in vitro the anti-inflammatory cytokine interleukin (IL)-10. To learn more about the coherence between IL-10 and proinflammatory cytokines in active sarcoidosis, the release of interferon (IFN)- γ, macrophage inhibitory protein (MIP)-1 α, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was studied and additionally compared to normal controls and patients with pneumonia and interstitial lung fibrosis. AM were obtained by bronchoalveolar lavage from 13 patients with active sarcoidosis, 8 patients with interstitial lung fibrosis, 10 patients with bacterial pneumonia, and 14 normal controls. The spontaneous and stimulated (tumor necrosis factor [TNF]- α, IL-1 β) cytokine release was measured in the supernatant of cultured AM by enzyme-linked immunosorbent assay (ELISA). Unstimulated AM from sarcoidosis patients released more IL-10, IFN- γ, MIP-1 α, and GM-CSF than normal controls and patients with pneumonia and interstitial lung disease. Stimulation with TNF- α or IL-1 β increased the MIP-1 α and GM-CSF release from AM of normal controls and patients with pneumonia and interstitial lung disease: however, no further enhancement of MIP-1 α and GM-CSF production was observed in AM from sarcoidosis patients. Exogenous IL-10 reduced the spontaneous and stimulated MIP-1 α and GM-CSF release in sarcoidosis to a lesser extent than in controls and patients with fibrosis and pneumonia. The up-regulated IL-10 in active pulmonary sarcoidosis may be a compensatory response to the enhanced expression of proinflammatory cytokines in order to down-regulate the inflammatory process. The results suggest an involvement of the anti-inflammatory cytokine IL-10 in the immunopathogenesis of sarcoidosis.