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

Background IL-10 exhibits anti-inflammatory effects on activated rodent mas t 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 h uman 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 medi ators is still unknown. Thus, the objective of this study was to investigat e the effects of IL-IO on the release of inflammatory mediators by IgE/anti -IgE-challenged human cord blood-derived mast cells (CBMC), used as an in v itro model of MC phenotypically similar to human lung MC. Materials and methods Highly purified human MC were obtained by a first ste p of longterm culture of cord blood mononuclear cells in the presence of hu man recombinant stem cell factor (rhSCF) and of human recombinant IL-6 (rhI L-6), followed by a second step of purification by depletion of contaminati ng cells with an immunomagnetic method. The cells were treated with human I gE, then challenged with anti-human IgE, in the presence or the absence of recombinant rhIL-10 used at various concentrations. Histamine, tumour necro sis factor-alpha (TNF-alpha), IL-5 and IL-8 were measured in the various su pernatants collected at different times after the beginning of the challeng e. Results IL-10 inhibited the release of TNF-alpha and of IL-8, but not of IL -5, by activated CBMC. Interestingly, IL-10 also inhibited the release of h istamine 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-alpha, IL-8 and histamine. These data provide new insights into the con trol of human mast cell activation and might lead to a better knowledge of the cellular mechanisms controlling allergic reactions.