Effects of histamine on Th1/Th2 cytokine balance

Kathleen A. Packard, Manzoor M. Khan

Research output: Contribution to journalReview articlepeer-review

112 Scopus citations

Abstract

Atopic asthma is a chronic inflammatory disorder of the airways where upon exposure to allergens, the body mounts an immune response. This disease is associated with an increase in the number of Th2 (T helper type 2) cells and Th2 cytokines and a decrease in the number of Th1 (T helper type 1) cells and Th1 cytokines. Histamine plays an important role in the pathogenesis of atopic asthma through differential regulation of T helper lymphocytes. Histamine enhances the secretion of Th2 cytokines such as IL-4 (interleukin-4), IL-5, IL-10 and IL-13 and inhibits the production of Th1 cytokines IL-2 and IFNγ (interferon-γ) and monokine IL-12. It has been shown that histamine can modulate the cytokine network through upregulation of PGE2 (prostaglandin E2) and NO (nitric oxide). Histamine also affects cytokine production via H2 receptors and through the activation of PKA (protein kinase A). We have also demonstrated that the Jak-STAT (Janus kinase-signal transducers and activators of transcription) pathway is involved in histamine-mediated regulation of Th2 cytokines IL-5, IL-10, IL-13 and Th1 cytokine IFNγ. While standard treatment of asthma consists of β-receptor agonists and inhaled corticosteroids, the elucidation of histamine's control over the cytokine network and the Th1/Th2 balance provides a basis for the potential use of antihistamines in the prevention and treatment of atopic asthma. Several other anti-allergic agents to modulate the Th1/Th2 balance are under current investigation based on this paradigm. These include cytokines, cytokine antagonists, anti-IgE, and vaccinations. As more advances are made in our understanding of histamine and its control over the Th1/Th2 balance, the use of new therapeutic targets such as these will play a prominent role in disease management.

Original languageEnglish (US)
Pages (from-to)909-920
Number of pages12
JournalInternational Immunopharmacology
Volume3
Issue number7
DOIs
StatePublished - Jul 2003

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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