IL-4 exacerbates anaphylaxis.
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.
Strait
Richard T
RT
Division of Emergency Medicine, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Morris
Suzanne C
SC
Smiley
Kristi
K
Urban
Joseph F
JF
Finkelman
Fred D
FD
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D000707:Anaphylaxis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D019559:Capillary Leak Syndrome / Q000097:blood / Q000276:immunology / Q000503:physiopathology; D004306:Dose-Response Relationship, Immunologic; D004359:Drug Therapy, Combination; D005260:Female; D007275:Injections, Intravenous; D018664:Interleukin-12 / Q000008:administration & dosage / Q000627:therapeutic use; D018793:Interleukin-13 / Q000009:adverse effects / Q000502:physiology; D020382:Interleukin-18 / Q000008:administration & dosage / Q000627:therapeutic use; D015847:Interleukin-4 / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D017997:Leukotriene C4 / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D010972:Platelet Activating Factor / Q000008:administration & dosage; D050800:STAT6 Transcription Factor; D012701:Serotonin / Q000008:administration & dosage; D015398:Signal Transduction / Q000276:immunology; D015534:Trans-Activators / Q000502:physiology
D000276:Adjuvants, Immunologic; D018793:Interleukin-13; D020382:Interleukin-18; D010972:Platelet Activating Factor; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D015847:Interleukin-4; D017997:Leukotriene C4; D012701:Serotonin