H. Renz et al., INHIBITION OF ALLERGEN-INDUCED IGE AND IGG1 PRODUCTION BY SOLUBLE IL-4 RECEPTOR, International archives of allergy and immunology, 106(1), 1995, pp. 46-54
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.