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United States Department of Agriculture

Agricultural Research Service

Title: Il-4 Exacerbates Anaphylaxis

Authors
item Strait, Richard - CHLDRN HOSP,CIN,OH
item Morris, Suzanne - UNIV OF CIN, OH
item Smiley, Kristi - CHLDRN HOSP,CIN,OH
item Urban, Joseph
item Finkelman, Fred - UNIV OF CIN, OH

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 1, 2003
Publication Date: April 1, 2003
Citation: Strait, R., Morris, S., Smiley, K., Urban Jr, J.F., Finkelman, F. 2003. Il-4 exacerbates anaphylaxis. Journal of Immunology. 170:3835-3842 (2003)

Interpretive Summary: The mechanism of response to worm parasites and to allergic substances parallels the production of a protein called IL-4 and a related substance called IL-13. These allergic substances produced by the body initiate reactions that change blood vessel permeability among other things leading to the release of materials from the blood and intestine that attempt to flush out noxious agents. This study was designed to determine if IL-4 and IL-13 enhanced the initial phases of the reactions to strengthen the level of the response to an allergen or worm infection. Mice were treated with either IL-4 or IL-13 and the extent of blood vessel permeability was measured after stimulating blood cells that release mediators of normal blood vessel permeability or following a parasitic infection. The results indicated that both of these substances enhanced the response to cell mediators and to infection leading to much stronger down steam reactions to allergens or worms. This information indicates that both IL-4 and IL-13 are target molecules to regulate if the level of response to these agents is needed. The work will benefit pharmaceutical companies that develop antagonists to reducesthe symptoms of allergy and to research personnel in academic, industry and government laboratories that are interested in better vaccines to control the level or intensity of parasitic infections.

Technical Abstract: Studies were established to determine if IL-4, a cytokine critical for inducing allergic responses, 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 FceRI or FcgRIII. This effect was inhibited by endogenously produced IFN-g, was T cell-, B cell-, and gamma chain-independent, and required IL-4Ra and Stat6. Stat6 and IL-4Ra 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 contribute to protective immunity against gastrointestinal worms and to allergic immunopathology.

Last Modified: 11/26/2014
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