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Published ahead of print on August 11, 2004, doi:10.1164/rccm.200404-533OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 11, December 2004, 1153-1157

A more recent version of this article appeared on December 1, 2004
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Submitted on May 11, 2004
Accepted on August 6, 2004

Immunostimulatory Oligonucleotides Attenuate Airways Remodelling in Allergic Monkeys

Michelle V Fanucchi1*, Edward S Schelegle1, Gregory L Baker1, Michael J Evans1, Ruth J McDonald1, Laurel J Gershwin1, Eyal Raz2, Dallas M Hyde1, Charles G Plopper1, and Lisa A Miller1

1 Center for Comparative Respiratory Biology and Medicine, California Primate Research Center, University of California, Davis, CA, USA, 2 School of Medicine, University of California, San Diego, CA, USA

* To whom correspondence should be addressed. E-mail: mvfanucchi{at}ucdavis.ed.

To determine whether inhaled immunostimulatory DNA sequence oligonucleotides containing CpG motifs mitigate the pathophysiologic manifestation of the asthmatic phenotype (airways hyperresponsiveness and airways remodelling), 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 2-fold in immunostimulatory DNA sequence-treated compared to 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 remodelling produced in non-human primates with experimentally-induced allergic airways disease.
Key words: immunostimulatory DNA sequence oligonucleotides, allergic asthma, airway wall alterations, non-human primate




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