Published ahead of print on March 30, 2006, doi:10.1164/rccm.200601-057OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200601-057OC
Immunostimulatory Sequences Regulate Interferon-inducible Genes but not Allergic Airway ResponsesMcMaster University, Hamilton, Ontario; Hopital Laval, Quebec City, Quebec, Canada; and Dynavax Technologies, Berkeley, California Correspondence and requests for reprints should be addressed to Paul O'Byrne, M.B., HSC 3W10, McMaster University, 1200 Main Street West, Hamilton, ON, Canada, L8N 3Z5. E-mail: obyrnep{at}mcmaster.ca Rationale: 1018 ISS is a synthetic oligonucleotide containing immunostimulatory CpG motifs. In animal studies, 1018 ISS effectively inhibited Th2-mediated lung inflammation, including eosinophil infiltration, and airway hyperresponsiveness. Objectives: To evaluate whether 1018 ISS has activity in subjects with allergic asthma. Methods: Forty subjects (n = 21, 1018 ISS; n = 19, placebo) were enrolled in a randomized, double-blind, placebo-controlled, parallel-group study to examine safety, pharmacologic activity, and efficacy of 1018 ISS on allergen-induced airway responses. Subjects received 36 mg of 1018 ISS or placebo by nebulization weekly for 4 wk. Measurements: Allergen inhalation challenge was performed 24 h after the 2nd and 4th doses to measure the early and late fall in FEV1. Sputum cells and peripheral blood mononuclear cells were collected before and after dosing, and gene expression was measured by quantitative polymerase chain reaction.
Main Results: Treatment with 1018 ISS significantly increased expression of interferon (IFN)- Conclusions: This study demonstrated that 1018 ISS is safe and pharmacologically active in the respiratory tract of asthmatics but, at this dose regimen, did not inhibit a fall in FEV1 or other key features of the response to inhaled allergen challenge. This suggests that induction of IFN and IFN-inducible genes alone is not sufficient to inhibit allergen-induced responses in asthmatic subjects.
Key Words: airway responses • allergen inhalation challenge • allergic asthma • gene expression, immunostimulatory CpG motifs This article has been cited by other articles:
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and IFN-inducible genes, such as IFN-
