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Immunostimulatory Oligonucleotides Attenuate Airways Remodeling in Allergic Monkeys

Center for Comparative Respiratory Biology and Medicine, California National Primate Research Center, University of California, Davis; and School of Medicine, University of California, San Diego, California

Correspondence and requests for reprints should be addressed to Michelle V. Fanucchi, Ph.D., Department of Anatomy, Physiology and Cell Biology, University of California, School of Veterinary Medicine, One Shields Avenue, Davis, CA 95616. E-mail: mvfanucchi{at}ucdavis.edu

To determine whether inhaled immunostimulatory DNA sequence oligonucleotides containing CpG motifs mitigate the pathophysiologic manifestation of the asthmatic phenotype (airways hyperresponsiveness and airways remodeling), rhesus monkeys with experimentally induced allergic airways disease were treated seven times with inhaled immunostimulatory oligonucleotides (or sham) periodically for 33 weeks. Airways hyperresponsiveness was reduced twofold in immunostimulatory DNA sequence–treated compared with sham-treated monkeys. Airways from immunostimulatory oligonucleotide-treated monkeys had thinner reticular basement membranes, fewer mucous cells, fewer eosinophils, and fewer mast cells than sham-treated allergic monkeys. We conclude that inhaled immunostimulatory oligonucleotides can attenuate the magnitude of airway hyperreactivity and airways remodeling produced in nonhuman primates with experimentally induced allergic airways disease.

Key Words: airway wall alterations • allergic asthma • immunostimulatory DNA sequence oligonucleotides • nonhuman primate

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