Increased spontaneous interleukin-10 release from alveolar macrophages in active pulmonary sarcoidosis.
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)-gamma, macrophage inhibitory protein (MIP)-1alpha, 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]-alpha, IL-1beta) 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-gamma, MIP-1alpha, and GM-CSF than normal controls and patients with pneumonia and interstitial lung disease. Stimulation with TNF-alpha or IL-1beta increased the MIP-1alpha and GM-CSF release from AM of normal controls and patients with pneumonia and interstitial lung disease: however, no further enhancement of MIP-1alpha and GM-CSF production was observed in AM from sarcoidosis patients. Exogenous IL-10 reduced the spontaneous and stimulated MIP-1alpha 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.
Oltmanns
Ute
U
Department of Pneumology, University Hospital Charité, Berlin, Germany.
Schmidt
Bernd
B
Hoernig
Soeren
S
Witt
Christian
C
John
Matthias
M
D000328:Adult; D018893:Bronchoalveolar Lavage; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor