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Cyclooxygenase inhibition augments allergic inflammation through CD4-dependent, STAT6-independent mechanisms

Koichi Hashimoto1, James R Sheller, Jason D Morrow

  • 1Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|December 22, 2004
PubMed

Insights

Nonselective cyclooxygenase (COX) inhibition exacerbates allergic lung inflammation, driven by CD4+ T cells. This effect is independent of IL-4 signaling, highlighting COX products

Area of Science:

  • Immunology
  • Allergic Inflammation
  • Pharmacology

Background:

  • Nonselective cyclooxygenase (COX) inhibition increases type 2 cytokines and lung eosinophilia in allergic disease models.
  • Mechanisms underlying COX inhibition-induced allergic inflammation remain unclear.

Purpose of the Study:

  • To investigate the mechanisms by which COX inhibition augments allergen-induced allergic inflammation.
  • To determine the role of CD4+ and CD8+ T cells and IL-4 signaling pathways in COX inhibition-mediated allergic responses.

Main Methods:

  • Murine model of allergic disease.
  • Antibody depletion of CD4+ and CD8+ T cells.
  • Analysis of IL-5, IL-13, and IgE levels.
  • Use of IL-4, IL-4Ralpha, and STAT6 knockout mice.

Main Results:

  • Heightened allergic inflammation due to COX inhibition was CD4+ T cell dependent, not CD8+ T cell dependent.
  • COX inhibition restored wild-type levels of IL-5 and IL-13 and increased eosinophilia in IL-4, IL-4Ralpha, and STAT6 knockout mice, indicating independence from this pathway.
  • COX inhibition increased IgE in wild-type mice, but not in knockout mice, suggesting IL-13 is not the sole switch for IgE synthesis.

Conclusions:

  • COX inhibition plays a central role in regulating allergic immune responses.
  • The augmentation of allergic inflammation by COX inhibition is independent of the IL-4/IL-4Ralpha/STAT6 signaling pathway.
  • IL-13 alone does not appear to be the sole switch factor for IgE synthesis in this allergic model.

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