ASNase-induced anaphylaxis exacerbation is due to higher IL-4/IL-13 in WT mice after immunization. (A) ASNase-immunized mice received 3 mg of anti-mouse IL-4Rα (M1) or an isotype-matched control mAb, were challenged the next day with 2 mg of histamine IV, and evaluated for the development of hypothermia. NFATC2 deficiency protects against histamine-induced anaphylaxis exacerbation in immunized mice, and the difference in anaphylaxis between WT and KO mice is abolished after blocking IL-4Rα. (B) Immunized KO mice are protected from passive ASNase IC–mediated anaphylaxis relative to controls when prepared at 5 µg of ASNase and 50 µg of purified anti-ASNase IgG, but not at a fivefold lower dose. *P < .05; **P < .01.