Interleukin-10 Secretion by Alveolar Macrophages and Monocytes in Sarcoidosis

Abstract

Background: Alveolitis and the production of proinflammatory cytokines are known features of sarcoidosis. Because of the usually spontaneous resolution of alveolitis despite local secretion of mediators causing inflammation and granuloma formation, we hypothesized that downmodulating mechanisms such as anti-inflammatory cytokines might be involved in this process. Objective: Investigation of the secretion of the macrophage deactivating cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) by alveolar macrophages in untreated sarcoidosis of the lung. Methods: Fourteen consecutive and untreated patients with pulmonary sarcoidosis and 18 volunteers underwent bronchoscopy. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and the secretion of IL-10 and TGF-β was studied. Results: Spontaneous IL-10 production by AM was found in 6 of 14 patients and in 2 of 18 controls. The IL-10 level of lipopolysaccharide-stimulated AM was significantly higher in patients. Monocytes secreted significantly more IL-10 than AM, but there was no difference between sarcoid and control monocytes. No difference was found in the secretion of TGF-β between patients and controls. Conclusion: Increased local secretion of IL-10 – but not TGF-β – may represent a downmodulating mechanism involved in the spontaneous resolution of alveolitis in sarcoidosis.

Serum Amyloid A Regulates Granulomatous Inflammation in Sarcoidosis through Toll-like Receptor-2

“…Thus, the experimental model supports the in vitro expression data that SAA contributes to the immunopathology in sarcoidosis. Although these effects of SAA on cytokine regulation are consistent with its role in other diseases, it is notable that our data, indicating that SAA stimulates the coordinated production of relevant immunoregulatory cytokines (TNF, IL-10, and IL-18) from lung macrophages in sarcoidosis, provides a specific innate effector pathway that can regulate local adaptive immunity in sarcoidosis and the formation of discrete, compact epithelioid granulomas characteristic of sarcoidosis (3,(5)(6)(7). The contributions of other relevant monokines such as IL-12 will be important to analyze in future studies, as well as the effect of SAA on Th1 responses.…”

CCL18 Production is Decreased in Alveolar Macrophages from Cigarette Smokers

“…From our perspective IL-10 production is possibly explaining the difference in CCL18 production following LPS stimulation. While monocytes produce high amounts of IL-10 following LPS stimulation, AM produce only marginal levels of IL-10 [26]. We and others have shown, that IL-10 is a potent inductor of CCL18 production [15,27].…”

Increased interleukin-13 expression in patients with sarcoidosis

“…Zissel et al 13 reported no spontaneous IL-10 release from BAL fluid cells of patients with sarcoidosis. In contrast, Bingisser et al 15 recently described increased local secretion of IL-10 from alveolar macrophages in sarcoidosis. The different results may derive from the cell populations studied (BAL cells or alveolar macrophages).…”