Abstract
We evaluated whether IL-4, a cytokine critical for inducing allergic responses, also contributes to the effector phase of allergy. Pretreatment of mice with IL-4 or the related cytokine, IL-13, rapidly and dramatically increased the severity of anaphylaxis induced by cross-linking Fc(epsilon)RI or FcgammaRIII. This effect was inhibited by endogenously produced IFN-gamma, was T cell-, B cell-, and common gamma-chain-independent, and required IL-4Ralpha and Stat6. IL-4Ralpha signaling also enhanced anaphylaxis in mice infected with a nematode parasite that stimulates IL-4/IL-13 production. IL-4 exacerbated anaphylaxis by acting synergistically with vasoactive mediators to increase vascular permeability. Synergy between IL-4 and vasoactive mediators during the effector phase of allergic inflammation may both contribute to allergic immunopathology and enhance protective immunity against gastrointestinal worms.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / adverse effects
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Adjuvants, Immunologic / antagonists & inhibitors
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Adjuvants, Immunologic / biosynthesis
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Adjuvants, Immunologic / physiology
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Anaphylaxis / immunology*
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Anaphylaxis / pathology
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Anaphylaxis / physiopathology
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Anaphylaxis / prevention & control
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Animals
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Capillary Leak Syndrome / blood
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Capillary Leak Syndrome / immunology
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Capillary Leak Syndrome / physiopathology
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Dose-Response Relationship, Immunologic
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Drug Therapy, Combination
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Female
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Injections, Intravenous
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Interleukin-12 / administration & dosage
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Interleukin-12 / therapeutic use
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Interleukin-13 / adverse effects
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Interleukin-13 / physiology
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Interleukin-18 / administration & dosage
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Interleukin-18 / therapeutic use
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Interleukin-4 / adverse effects*
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Interleukin-4 / antagonists & inhibitors
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Interleukin-4 / biosynthesis
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Interleukin-4 / physiology*
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Leukotriene C4 / administration & dosage
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Nude
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Mice, Transgenic
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Platelet Activating Factor / administration & dosage
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STAT6 Transcription Factor
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Serotonin / administration & dosage
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Signal Transduction / immunology
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Trans-Activators / physiology
Substances
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Adjuvants, Immunologic
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Interleukin-13
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Interleukin-18
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Platelet Activating Factor
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STAT6 Transcription Factor
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Stat6 protein, mouse
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Trans-Activators
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Interleukin-12
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Interleukin-4
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Leukotriene C4
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Serotonin