Inhibition of IgE‐induced activation of human mast cells by IL‐10

Abstract

Background IL‐10 exhibits anti‐inflammatory effects on activated rodent mast cells (MC) in vitro and inhibits allergen‐induced airway inflammation in vivo in murine models. The effects of IL‐10 on the allergic activation of human MC are presently unknown. Objective In light of the well‐known heterogeneity of mast cell reactivity between animal species, one cannot readily predict the response of human MC to IL‐10. Moreover, the impact of IL‐10 on MC‐derived proinflammatory mediators is still unknown. Thus, the objective of this study was to investigate the effects of IL‐10 on the release of inflammatory mediators by IgE/anti‐IgE‐challenged human cord blood‐derived mast cells (CBMC), used as an in vitro model of MC phenotypically similar to human lung MC. Materials and methods Highly purified human MC were obtained by a first step of long‐term culture of cord blood mononuclear cells in the presence of human recombinant stem cell factor (rhSCF) and of human recombinant IL‐6 (rhIL‐6), followed by a second step of purification by depletion of contaminating cells with an immunomagnetic method. The cells were treated with human IgE, then challenged with anti‐human IgE, in the presence or the absence of recombinant rhIL‐10 used at various concentrations. Histamine, tumour necrosis factor‐alpha (TNF‐α), IL‐5 and IL‐8 were measured in the various supernatants collected at different times after the beginning of the challenge. Results IL‐10 inhibited the release of TNF‐α and of IL‐8, but not of IL‐5, by activated CBMC. Interestingly, IL‐10 also inhibited the release of histamine by activated CBMC, contrasting with data reported for rodent MC. Conclusions These findings suggest that IL‐10 might have anti‐inflammatory effects on IgE/anti‐IgE‐challenged human MC by inhibiting their release of TNF‐α, IL‐8 and histamine. These data provide new insights into the control of human mast cell activation and might lead to a better knowledge of the cellular mechanisms controlling allergic reactions.