Text Box: LONG-TERM INHIBITION OF AIRWAYS EOSINOPHILIA BY ADMINISTRATION OF A SINGLE DOSE OF CpG OLIGODEOXYNUCLEOTIDES IN MICE
Choi S-M, Li C, Simons FER, HayGlass KT, Peng Z
University of Manitoba, Winnipeg, Canada

Background:  Unmethylated CpG motifs in bacterial DNA or synthesized oligodeoxynucleotides (CpG ODN) have been shown to downregulate allergic responses by switching immune response towards a dominant Th1 response. We have previously found that intranasal administration of CpG ODN inhibits subsequent airways eosinophilia in mice with established airways inflammation (Choi et al. J Allergy Clin Immunol 2001;107:S67). 
Objectives: In this study we wanted to investigate how long this inhibition would last after administration of a single dose of CpG ODNs.
Methods: Mice were sensitized by intradermal injections of ovalbumin twice weekly throughout the study. At week 4, airways inflammation was induced by intranasal (i.n.) challenge with ovalbumin. After a 4-week rest, at week 8, the mice were challenged i.n. again with ovalbumin in the presence of either CpG ODN or control ODN. Three, twenty four and forty five days later, bronchoalveolar lavage fluid (BALF) eosinophils were counted. Ovalbumin-induced cytokine production by spleen cells and serum specific IgE and IgG2a were measured by ELISA.
Results:  BALF eosinophils were significantly reduced in the CpG ODNs-treated mice (15% at day 3) compared to the control mice (47%). The inhibition of airway eosinophilia lasted at least 45 days (p¡¯s < 0.01). Serum IgE decreased transiently at day 3 and IgG2a significantly increased at days 24 and 45 after CpG administration. Cytokine analysis revealed decreased production of IL-4, IL-5 and increased production of IL-12 and IFN  in the treated group as compared to the control group.   
Conclusion:  CpG ODN vaccination is a potentially useful approach for long-term reversal of airways eosinophilia in asthmatic mice.
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