INHIBITION OF ALLERGEN-INDUCED IGE AND IGG1 PRODUCTION BY SOLUBLE IL-4 RECEPTOR

In this study, the effect of soluble IL-4 receptors (sIL-4R) on murine allergen-induced IgE and IgG1 production was examined. Lymphocytes fr om mice sensitized to the allergens ragweed (RW) or ovalbumin (OVA) in vivo were restimulated in vitro with the sensitizing allergen in the presence of either a soluble murine sIL-4R, a dimeric sIL-4R Ig fusion protein (sIL-4R/Fc), or anti-IL-4, antibody in 14-day cultures. Both monomeric and dimeric sIL-4R inhibited polyclonal IgE (similar to 70%) and IgG1 (similar to 35%) production in a dose-dependent fashion, sim ilar to that observed in the presence of the anti-IL-4 antibody. Aller gen-specific IgE and IgG1 were inhibited to a greater degree. Addition of sIL-4R was most effective when present in the culture during the f irst 3 days and added not later than day 6. In kinetic experiments, we distinguished ongoing IgE production from precommitted B cells versus newly induced IgE synthesis and found that newly induced IgE producti on was the major target of the sIL-4Rs. These data demonstrate the eff icacy of sIL-4R in inhibiting the early stages of the IgE B-cell matur ation pathway and indicate the potential of sIL-4R for the inhibition of IgE production in vivo.