CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma

J Allergy Clin Immunol. 1999 Dec;104(6):1258-64. doi: 10.1016/s0091-6749(99)70022-9.

Abstract

Background: Oligodeoxynucleotides (ODNs) containing the dinucleotide CpG in a specific sequence context (CpG-ODNs) have the ability to prevent the development of eosinophilic airway inflammation and bronchial hyperreactivity in a murine model of asthma. We have previously demonstrated that CpG-ODNs stimulate expression of the T(H1)-inducing cytokines IFN-gamma and IL-12 in a murine model of asthma and that this stimulation is associated with the protection against asthmatic inflammation.

Objective: The purpose of this study was to examine whether the protection conferred by CpG-ODNs in a schistosome egg-egg antigen murine model of asthma is dependent on the induction of IFN-gamma, IL-12, or both.

Methods: C57BL/6 mice were sensitized to schistosome eggs in the presence or absence of CpG-ODNs or control ODNs and then stimulated with soluble egg antigen in the airway. The protection offered by CpG-ODNs in these mice was compared with the protection induced by CpG-ODNs in IL-12 and IFN-gamma knockout mice and in mice treated with anticytokine blocking antibodies. Double-knockout mice (IL-12/IFN-gamma) were also generated and used in these studies. Determinations included airway eosinophilic inflammation and bronchial hyperreactivity to inhaled methacholine.

Results: We found that CpG-ODNs confer protection against both airway eosinophilia and bronchial hyperreactivity in the absence of IFN-gamma or IL-12 or in the presence of both cytokines together. However, in the absence of either IL-12 or IFN-gamma, mice require 10 times as much CpG-ODNs to be protected against the induction of airway eosinophilia. The T(H2) cytokines IL-4 and IL-5 were reduced in all of the CpG-treated mice, although less in the absence of IL-12 and IFN-gamma.

Conclusion: These data indicate that CpG-ODNs prevent the generation of T(H2)-like immune responses by multiple mechanisms, which involve, but do not require, IL-12 and IFN-gamma. A direct suppressive effect of CpG-ODNs on T(H2) responses is suggested by their reduction in IFN-gamma and IL-12 knockout mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Asthma / physiopathology
  • Asthma / prevention & control
  • Bronchial Hyperreactivity / prevention & control
  • CpG Islands / physiology*
  • Cytokines / physiology*
  • Disease Models, Animal
  • Eosinophilia / prevention & control
  • Female
  • Inflammation / prevention & control
  • Interferon-gamma / physiology
  • Interleukin-12 / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Respiratory Tract Diseases / prevention & control
  • Th1 Cells / chemistry
  • Th2 Cells / chemistry

Substances

  • Cytokines
  • Interleukin-12
  • Interferon-gamma