Interferon‐γ inhibits serotonin release from mouse peritoneal mast cells

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Abstract
Conditioned medium (CM) from concanavalin A‐activated mouse spleen cells inhibits antigen‐induced 5‐hydroxytryptamine (5‐HT) release from mouse peritoneal mast cells when added for 24 or 48 h to cell cultures containing monoclonal IgE sensitizing antibody. We present the following evidence that the spleen cell‐derived inhibitory factor is interferon‐γ (IFN‐γ): (a) CM from Con A‐activated spleen cells and from Chinese hamster ovary (CHO) cells transfected with the murine (Mu)IFN‐γ gene both produced a graded inhibition of 5‐HT release when added to peritoneal cell cultures containing IgE and subsequently challenged with antigen; (b) the relative inhibitory potency of the two preparations corresponded to their relative IFN content as determined by antiviral bioassay; (c) the inhibitory activity of spleen cell CM and of CM from IFN‐γ gene‐transfected CHO cells was abolished by treatment with a rat monoclonal MuIFN‐γ‐neutralizing antibody, i.e. 5‐HT release returned to control levels, and (d) a highly immunopurified preparation of recombinant MuIFN‐γ retained the inhibitory activity, and was active at concentrations as low as 2 U/ml. The inhibitory activity of IFN‐γ appeared to be a direct effect of the cytokine on mast cells, since CM generated for different time periods from unfractionated peritoneal cells treated with purified recombinant MuIFN‐γ contained no inhibitory activity other than IFN‐γ itself, as demonstrated by neutralization of the cytokine with monoclonal antibody. Furthermore, purified recombinant MuIFN‐γ was equally active on mast cells enriched by density centrifugation up to 95% purity as on unfractionated peritoneal cells (1%–2% mast cells). Purified recombinant MuIFN‐γ inhibited 5‐HT release induced by a range of different cell activators, namely antigen, anti‐IgE, compound 48/80 and calcium ionophore A23187. Hence inhibition is not specific to IgE‐dependent activation of mast cells, but seems to be directed more generally at the secretory process of these cells.

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