Use of CpG oligonucleotides in treatment of asthma and allergic disease.

Full Abstract

In the last several decades, there has been a marked increase in the prevalence of atopic disorders including asthma in "Western" societies; a relationship has been identified between lack of early-life exposure to microbes or microbial products and increased susceptibility to atopic disorders. The innate immune system is activated by early microbial exposures, many of which utilize one of the Toll-like receptors, and there has been significant interest in studying how ligation of TLRs may be therapeutically useful. CpG oligonucleotides (CpG-ODN, resembling bacterial DNA) engage TLR-9 on B-cells, dendritic cells and other cell types, resulting in a cascade that includes induction of Th1-type and T-regulatory-type immune responses. Preclinical models of asthma have demonstrated that CpG-ODN are potent inhibitors of atopic responses, suppressing Th2 cytokine and, reducing airway eosinophilia, systemic levels of IgE, and bronchial hyperreactivity-in short the critical attributes of the asthmatic phenotype. In models of chronic allergen exposure, CpG-ODN are also effective at preventing the development of airway remodeling. In established asthma, CpG-ODN can reverse manifestations of disease, both when used alone or in combination with allergen immunotherapy. Early clinical trials have had mixed results, including a significant benefit when CpG-ODN were conjugated to ragweed allergen in an allergic rhinitis immunotherapy study, but only limited efficacy seen when administered prior to allergen challenge in asthmatics. Further study of CpG-ODNs for the treatment of asthma and other atopic disorders is warranted by existing data.

Author information

Author/s: Fonseca, David E (DE); Kline, Joel N (JN);

Affiliation: Roy J. and Lucille A. Carver College of Medicine, University of Iowa, USA.

Journal and publication information

Publication Type: Journal Article; Review

Journal: Advanced drug delivery reviews (Adv Drug Deliv Rev), published in Netherlands. (Language: eng)

Reference: 2009-Mar; vol 61 (issue 3) : pp 256-62

Dates: Created 2009/03/16; Completed 2009/07/15;

PMID: 19167442, status: MEDLINE (last retrieved date: 7/24/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adjuvants, Immunologic - therapeutic use
Animals
Anti-Allergic Agents - therapeutic use
Anti-Asthmatic Agents - therapeutic use
Asthma - drug therapy; immunology; metabolism
CpG Islands
Cytokines - immunology; metabolism

Cytokines - immunology; metabolism
Humans
Hypersensitivity, Immediate - drug therapy; immunology; metabolism
Immunotherapy
Oligodeoxyribonucleotides - therapeutic use
Th1 Cells - immunology
Th2 Cells - immunology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Adjuvants, Immunologic (0) ; Anti-Allergic Agents (0) ; Anti-Asthmatic Agents (0) ; CPG-oligonucleotide (0) ; Cytokines (0) ; Oligodeoxyribonucleotides (0)

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