Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice

Stephen H. Gavett, Daniel J. O’Hearn, Xiumin Li, Shau Ku Huang, Fred D. Finkelman, Marsha Wills-Karp

Research output: Contribution to journalArticle

566 Citations (Scopus)

Abstract

Allergic asthma is characterized by airway hyperresponsiveness and pulmonary eosinophilia, and may be mediated by T helper (Th) lymphocytes expressing a Th2 cytokine pattern. Interleukin (IL) 12 suppresses the expression of Th2 cytokines and their associated responses, including eosinophilia, serum immunoglobulin E, and mucosal mastocytosis. We have previously shown in a routine model that antigen-induced increases in airway hyperresponsiveness and pulmonary eosinophilia are CD4+ T cell dependent. We used this model to determine the ability of IL-12 to prevent antigen-induced increases in airway hyperresponsiveness, bronchoalveolar lavage (BAL) eosinophils, and lung Th2 cytokine expression. Sensitized A/J mice developed airway hyperresponsiveness and increased numbers of BAL eosinophils and other inflammatory cells after single or repeated intratracheal challenges with sheep red blood cell antigen. Pulmonary mKNA and protein levels of the Th2 cytokines IL-4 and IL-5 were increased after antigen challenge. Administration oflL-12 (1 µg/d x 5 d) at the time of a single antigen challenge abolished the airway hyperresponsiveness and pulmonary eosinophilia and promoted an increase in interferon (IFN) γ and decreases in IL-4 and IL-5 expression. The effects of IL-12 were partially dependent on IFN-γ, because concurrent treatment with IL-12 and anti-IFN-γmonoclonal antibody partially reversed the inhibition of airway hyperresponsiveness and eosinophilia by IL-12. Treatment of mice with IL-12 at the time of a second antigen challenge also prevented airway hyperresponsiveness and significantly reduced numbers of BAL inflammatory cells, reflecting the ability of IL-12 to inhibit responses associated with ongoing antigen-induced pulmonary inflammation. These data show that antigen-induced airway hyperresponsiveness and inflammation can be blocked by IL-12, which suppresses Th2 cytokine expression. Local administration of IL-12 may provide a novel immunotherapy for the treatment of pulmonary allergic disorders such as atopic asthma.

Original languageEnglish
Pages (from-to)1527-1536
Number of pages10
JournalJournal of Experimental Medicine
Volume182
Issue number5
DOIs
Publication statusPublished - Nov 1 1995
Externally publishedYes

Fingerprint

Interleukin-12
Cytokines
Inflammation
Antigens
Pulmonary Eosinophilia
Bronchoalveolar Lavage
Interferons
Interleukin-5
Eosinophilia
Eosinophils
Interleukin-4
Lung
Asthma
Mastocytosis
Helper-Inducer T-Lymphocytes
Immunotherapy
Immunoglobulin E
Sheep
Pneumonia
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice. / Gavett, Stephen H.; O’Hearn, Daniel J.; Li, Xiumin; Huang, Shau Ku; Finkelman, Fred D.; Wills-Karp, Marsha.

In: Journal of Experimental Medicine, Vol. 182, No. 5, 01.11.1995, p. 1527-1536.

Research output: Contribution to journalArticle

Gavett, Stephen H. ; O’Hearn, Daniel J. ; Li, Xiumin ; Huang, Shau Ku ; Finkelman, Fred D. ; Wills-Karp, Marsha. / Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice. In: Journal of Experimental Medicine. 1995 ; Vol. 182, No. 5. pp. 1527-1536.
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