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

Autor:	Campbell JD; Dynavax Technologies, Berkeley, CA 94710., Kell SA; Dynavax Technologies, Berkeley, CA 94710., Kozy HM; Dynavax Technologies, Berkeley, CA 94710., Lum JA; Dynavax Technologies, Berkeley, CA 94710., Sweetwood R; Dynavax Technologies, Berkeley, CA 94710., Chu M; Dynavax Technologies, Berkeley, CA 94710., Cunningham CR; Dynavax Technologies, Berkeley, CA 94710., Salamon H; Knowledge Synthesis, Berkeley, CA 94710., Lloyd CM; Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London SW7 2AZ UK., Coffman RL; Dynavax Technologies, Berkeley, CA 94710., Hessel EM; Dynavax Technologies, Berkeley, CA 94710.
Jazyk:	angličtina
Zdroj:	Thorax [Thorax] 2014 Jun; Vol. 69 (6), pp. 565-573. Date of Electronic Publication: 2014 Jan 24.
DOI:	10.1136/thoraxjnl-2013-204605
Abstrakt:	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. (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.)
Databáze:	MEDLINE
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