Novel immunomodulatory oligonucleotides prevent development of allergic airway inflammation and airway hyperresponsiveness in asthma

Devendra K. Agrawal, Jehad Edwan, Ekambar R. Kandimalla, Dong Yu, Lakshmi Bhagat, Daqing Wang, Sudhir Agrawal

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Oligodeoxynucleotides containing unmethylated CpG motifs (CpG oligos) have been shown to prevent development of allergic airway inflammation and airway hyperresponsiveness (AHR) in mouse models of asthma. Recently, we reported immunomodulatory oligonucleotides (IMOs) containing novel structures (immunomers) and synthetic immunostimulatory CpR (R=2′-deoxy-7- deazguanosine) motifs show potent stimulatory activity with distinct cytokine secretion profiles. Since type 2 T cells predominate in asthma and increase in type 1 cells can prevent the differentiation of naïve T lymphocytes to a type 2 phenotype, we hypothesized that IMOs can prevent the development of allergic airway inflammation and AHR in the ovalbumin (OVA)-sensitized and challenged mouse model. We found that co-administration of novel IMOs during OVA-sensitization abrogated both early and late allergic responses (LARs). AHR to methacholine was also blocked with IMO treatment. Analysis of bronchoalveolar lavage (BAL) fluid of mice treated with IMOs demonstrated complete reduction in eosinophils, with concomitant decreases in both serum and BAL fluid IL-4, IL-5, and IL-6 levels. In addition, there was a significant reduction in serum IL-10 levels. IMOs, in general, significantly attenuated the rise in serum IgE levels. In comparison, IMOs showed a significantly more potent effect on early and late allergic response than a conventional CpG oligo in this model. These data suggest that the treatment with these novel IMOs prevents OVA-induced allergic airway inflammation and AHR in asthma in the mouse and may provide a useful agent in the treatment of human asthma.

Original languageEnglish
Pages (from-to)127-138
Number of pages12
JournalInternational Immunopharmacology
Volume4
Issue number1
DOIs
StatePublished - Jan 2004

Fingerprint

Oligonucleotides
Asthma
Inflammation
Ovalbumin
Bronchoalveolar Lavage Fluid
Serum
T-Lymphocytes
Methacholine Chloride
Oligodeoxyribonucleotides
Interleukin-5
Eosinophils
Interleukin-4
Interleukin-10
Immunoglobulin E
Interleukin-6
Therapeutics
Cytokines
Phenotype

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology

Cite this

Novel immunomodulatory oligonucleotides prevent development of allergic airway inflammation and airway hyperresponsiveness in asthma. / Agrawal, Devendra K.; Edwan, Jehad; Kandimalla, Ekambar R.; Yu, Dong; Bhagat, Lakshmi; Wang, Daqing; Agrawal, Sudhir.

In: International Immunopharmacology, Vol. 4, No. 1, 01.2004, p. 127-138.

Research output: Contribution to journalArticle

Agrawal, Devendra K. ; Edwan, Jehad ; Kandimalla, Ekambar R. ; Yu, Dong ; Bhagat, Lakshmi ; Wang, Daqing ; Agrawal, Sudhir. / Novel immunomodulatory oligonucleotides prevent development of allergic airway inflammation and airway hyperresponsiveness in asthma. In: International Immunopharmacology. 2004 ; Vol. 4, No. 1. pp. 127-138.
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