IL-12/IL-13 axis in allergic asthma

Research output: Contribution to journalArticle

Abstract

Allergic airway diseases are associated with skewed TH2 cytokine production, although the underlying cause of this aberrant immune response is not well understood. Recently, 2 double-digit cytokines, IL-12 and IL-13, have been proposed to play pivotal roles in the TH2-polarized immune response to inhaled allergens. IL-12 is a critical determinant of TH1-mediated immune responses, and it has been shown that deficiency in this cytokine can lead to TH2-polarized immune responses. IL-13, on the other hand, has recently been shown to be a critical mediator of the effector arm of the allergic response. Overproduction of this cytokine has been shown to induce many common features of the allergic diathesis, such as airway hyperresponsiveness, eosinophilic inflammation, IgE production, mucus hypersecretion, and subepithelial fibrosis. Substantial evidence suggests that an imbalance in the production of these 2 critical immunoregulatory cytokines occurs in the lungs of atopic and asthmatic individuals, such that IL-13 is overproduced, and IL-12 production is impaired. As a result of this imbalance, IL-13 production may go unchecked and induce the classical allergic phenotype. Although it is not entirely clear what tips the balance between these 2 cytokines, genetic studies suggest that this could indeed be a primary event. Interestingly, the genes encoding both of these cytokines reside within the chromosomal regions on 5q, which have been associated with asthma in many populations. Although no evidence exists to date to support an association between asthma and polymorphisms in the IL12 gene, evidence is accumulating that supports an association between genetic alterations in the IL13 gene and atopy and asthma. From these observations, we can conclude that an imbalance in the IL-12/IL-13 axis may contribute to the development of allergic diseases, such as asthma. Studies to more fully examine the yin-yang relationship between these 2 critical immunoregulatory cytokines are clearly warranted.

Original languageEnglish (US)
Pages (from-to)9-18
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume107
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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Keywords

  • Allergy
  • Asthma
  • Cytokine
  • T-cell differentiation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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