Reciprocal regulation of cultured human mast cell cytokine production by IL-4 and IFN-γ

Abstract Background: T H 1 and T H 2 cytokines are thought to regulate allergic inflammation. Objective: Two key regulatory cytokines, IL-4 and IFN-γ, were examined for their effects on cytokine production by cultured human mast cells (CHMCs). Methods: CHMCs were obtained by culturing cord blood–derived CD34 + cells in the presence of stem cell factor and IL-6 for 14 to 16 weeks. CHMCs were passively sensitized with human myeloma IgE and supplemented with or without IL-4 or IFN-γ. After the sensitization, CHMCs were stimulated with anti-FcϵRIα mAb. Concentrations of secreted cytokines were measured by using ELISA, and cytokine messenger RNA was analyzed by using quantitative competitive RT-PCR. Results: IL-4 profoundly enhanced FcϵRI-mediated production of macrophage inflammatory protein (MIP) 1α, IL-8, and GM-CSF. For example, the enhancement by IL-4 (10 ng/mL) of the production of MIP-1α, IL-8, and GM-CSF was 25-, 7-, and 90-fold, respectively, after 6 hours. IL-4 also enhanced levels of FcϵRI-induced cytokine messenger RNA but to a lesser degree. In contrast, IFN-γ inhibited FcϵRI-induced production of MIP-1α, IL-8, and GM-CSF. For example, the inhibition by IFN-γ (10 ng/mL) of FcϵRI-mediated production of MIP-1α, IL-8, and GM-CSF was 80%, 75%, and 95%, respectively. IFN-γ also suppressed FcϵRI-induced messenger RNA expression of these cytokines. Neither IL-4 nor IFN-γ affected the kinetics of cytokine production by CHMCs. Conclusion: These data suggest that IL-4 and IFN-γ may influence allergic reactions by modulating human mast cell cytokine production. (J Allergy Clin Immunol 2000;106:141-9.)