IL-10-producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients.

BACKGROUND: Recently the immune regulatory role of T cell-derived IL-10 in allergic disease has been extensively studied. In contrast, there is mounting evidence that IL-10 might also have a role in the perpetuation of allergic inflammation and fibrotic remodeling. It has been reported that alternatively (IL-4) activated macrophages (aaMPhi) produce large quantities of IL-10 and lack IL-12 production. OBJECTIVE: Bearing this in mind, we hypothesized whether functionally different properties of IL-10-producing monocytes could be identified. METHODS: Intracellular cytokine expression of IL-10, IL-12, and IL-6 in peripheral blood CD14(+) monocytes was measured in 19 atopic patients and 18 healthy control subjects by means of flow cytometry. In addition, IL-10-secreting monocytes were sorted by means of flow cytometry. Capabilities of these cells regarding further differentiation, accessory cell capacity, and surface molecule expression were analyzed. RESULTS: Our data show a dichotomous expression pattern of either IL-10 or IL-12p40/p70 in peripheral blood monocytes after LPS stimulation. Compared with healthy control subjects, the percentage of IL-10-producing monocytes was significantly increased in atopic patients. IL-10-secreting monocytes were isolated by using an IL-10 secretion assay, and functional analysis of these sorted cells revealed that IL-10-secreting monocytes preferentially differentiate into suppressor of cytokine signaling 3 expressing aaMPhi, which perpetuate T(H)2 immune response. CONCLUSION: Our study shows the existence of an IL-10-producing monocyte subset, which is increased in atopic disease and which might facilitate allergic inflammation and fibrotic remodeling by differentiation into aaMPhi. CLINICAL IMPLICATIONS: Controlling aaMPhi in T(H)2-driven inflammatory processes might be a novel target for intervention strategies.