Effect of IL-4 and interferon-gamma (IFN-gamma) on IL-3- and IL-5-induced eosinophil differentiation from human cord blood mononuclear cells.

IL-4 and IFN-gamma positively and negatively regulate allergic inflammation. To determine the regulatory mechanisms of eosinopoiesis by cytokines, we examined the effect of recombinant IL-4 and IFN-gamma and of anti-IL-4 and anti-IFN-gamma antibodies on IL-3- and IL-5-induced eosinophil differentiation from human umbilical cord blood mononuclear cells. rhIL-4 (10-300 U/ml) inhibited IL-3- and IL-5-induced eosinophil differentiation from cord blood mononuclear cells on day 28 of culture by 62-81% in a concentration-dependent manner. rhIFN-gamma (5-500 U/ml) also inhibited IL-3- and IL-5-induced eosinophil differentiation by 80-99% in a concentration-dependent manner. The inhibitory effect of rhIL-4 and rhIFN-gamma was observed only when rhIL-4 or rhIFN-gamma were present in the culture from day 0 to day 14, but not from day 15 to day 28. Addition of anti-IL-4 antibody to the culture enhanced IL-3- and IL-5-induced eosinophil differentiation on day 28 of culture by 30%, whereas anti-IL-2 MoAb and anti-IFN-gamma MoAb had no significant effect. These results indicate that IL-4 and IFN-gamma have inhibitory effects on IL-3- and IL-5-induced eosinophil differentiation from its progenitor cells.