Kinetics of IL-10 production after segmental antigen challenge of atopic asthmatic subjects

Abstract

Background: IL-10 is an anti-inflammatory cytokine made by lymphocytes monocytes-macrophages and eosinophils and it may have an important role in regulating the asthmatic inflammatory response. IL-10 levels have been reported to be reduced in asthmatic airways potentially contributing to more intense inflammation. Objective: We sought to determine whether IL-10 levels were deficient in patients with mild asthma compared with controls and to determine whether IL-10 levels were associated with the resolution of eosinophilic inflammation. Methods: We quantified IL-10 levels in the bronchoalveolar lavage (BAL) fluid (ELISA) BAL cells (quantitative immunocytochemistry) purified alveolar macrophages-monocytes studied ex vivo (ELISA) before (day 1) and after (24 hours [day 2] 1 week [day 9] and 2 weeks [day 16]) segmental antigen challenge (SAC) and investigated the effect of glucocorticoid treatment on ex vivo macrophage-monocyte IL-10 production. Results: IL-10 levels were significantly higher in the BAL fluid of mild asthmatic subjects who demonstrated a dual reaction (both early and late) after whole lung ragweed inhalation challenge compared with nonallergic nonasthmatic control subjects before and 24 hours and 1 week after SAC. Macrophages-monocytes obtained before and after SAC from asthmatic patients also secreted increased amounts of IL-10 ex vivo than those from controls. Dexamethasone did not significantly change spontaneous IL-10 secretion from macrophages-monocytes in vitro. Quantitative immunocytochemical analysis of BAL cells demonstrated increased IL-10 in macrophages 24 hours after SAC and a similar trend in eosinophils. Conclusion: IL-10 is not deficient in mild asthma. Furthermore BAL IL-10 levels are significantly higher in asthmatic subjects with a dual response than in control subjects before and after SAC. The increase in IL-10 was coincident with the initial increase in BAL eosinophils although BAL eosinophilia persisted after IL-10 levels had returned to baseline suggesting that the increased IL-10 levels could not promptly terminate this localized eosinophilic response.