A limited CpG-containing oligodeoxynucleotide therapy regimen induces sustained suppression of allergic airway inflammation in mice.

Abstract

BACKGROUND:

CpG-containing oligodeoxynucleotides (CpG-ODNs) are potent inhibitors of T helper 2 mediated allergic airway disease in sensitised mice challenged with allergen. A single treatment has transient effects but a limited series of treatments has potential to achieve clinically meaningful sustained inhibition of allergic airway disease.

OBJECTIVE:

To optimise the treatment regimen for sustained efficacy and to determine the mechanisms of action in mice of an inhaled form of CpG-ODN being developed for human asthma treatment.

METHODS:

We set up a chronic allergic-asthma model using ragweed-sensitised mice exposed weekly to intranasal ragweed. Using this model, the effects of a limited series of weekly intranasal 1018 ISS (CpG-ODN; B-class) treatments were evaluated during treatment and for several weeks after treatments had stopped but weekly allergen exposures continued. Treatment efficacy was evaluated by measuring effects on lung T helper 2 cytokines and eosinophilia, and lung dendritic cell function and T-cell responses.

RESULTS:

Twelve intranasal 1018 ISS treatments induced significant suppression of bronchoalveolar lavage eosinophilia and interleukin 4, 5 and 13 levels. This suppression of allergic T helper 2 parameters was maintained through 13 weekly ragweed exposures administered after treatment cessation. Subsequent experiments demonstrated that at least five treatments were required for lasting suppression. Although CpG-ODN induced moderate T helper 1 responses, suppression of allergic airway disease did not require interferon γ but was associated with induction of a regulatory T-cell response.

CONCLUSIONS:

A short series of CpG-ODN treatments results in sustained suppression of allergic lung inflammation induced by a clinically relevant allergen.

• Authors: John D Campbell, Sariah A Kell, Heather M Kozy, Jeremy A Lum, Rosemary Sweetwood, Mabel Chu, Cameron R Cunningham, Hugh Salamon, Clare M Lloyd, Robert L Coffman, Edith M Hessel
• Journal: Thorax (Thorax) Vol. 69 Issue 6 Pg. 565-573 (Jun 2014) ISSN: 1468-3296 [Electronic] England
• PMID: 24464743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Allergens
• CPG-oligonucleotide
• Oligodeoxyribonucleotides

Topics

• Allergens
• Ambrosia
• Animals
• Bronchoalveolar Lavage Fluid (immunology)
• Disease Models, Animal
• Drug Administration Schedule
• Female
• Lung (immunology)
• Mice
• Mice, Inbred BALB C
• Oligodeoxyribonucleotides (administration & dosage)
• Respiratory Hypersensitivity (immunology, prevention & control)
• Th2 Cells (cytology, drug effects, immunology)