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Nasal IL-12p70 DNA Prevents and Treats Intestinal Allergic Diarrhea¹

Ayako Hino^*,,, Satoshi Fukuyama^*,, Kosuke Kataoka, Mi-Na Kweon^,, Kohtaro Fujihashi and Hiroshi Kiyono^2,*,,

^* Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, and Core Research for Evolutional Science and Technology (CREST) Program, Japan Science and Technology Corporation, Tokyo, Japan; Departments of Pediatric Dentistry and Microbiology, Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, AL 35294; and Mucosal Immunology Section, International Vaccine Institute, Seoul, Korea

OVA-induced allergic diarrhea occurs as a consequence of over-expression of Th1 inhibitory IL-12p40 monomers and homodimers in the large intestine, establishing a dominant Th2-type environment. In this study, we demonstrate that intranasally administered murine IL-12p70 naked DNA expression plasmids resulted in the synthesis of corresponding cytokine in the large intestinal CD11c⁺ dendritic cells, leading to the inhibition of Ag-specific Th2-type response for the prevention of allergic diarrhea and the suppression of clinical symptoms including OVA-specific IgE Ab synthesis. The nasal IL-12p70 DNA treatment proved effective even after the establishment of allergic diarrhea. These results suggest that the mucosal administration of naked IL-12p70 DNA plasmid should be considered as a possible preventive and therapeutic treatment for Th2 cell-mediated food allergic diseases in the intestinal tract.

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