Allergy Asthma Immunol Res.  2013 Jul;5(4):197-206. 10.4168/aair.2013.5.4.197.

Effects of Interleukin-9 Blockade on Chronic Airway Inflammation in Murine Asthma Models

Affiliations
  • 1Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi, Korea.
  • 2Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea. soyounwoo@ewha.ac.kr
  • 3Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.

Abstract

PURPOSE
Asthma is a chronic inflammatory disease of the airways associated with structural changes and airway remodeling. Interleukin (IL)-9 has pleiotropic effects on both inflammatory cells and airway structural cells, which are involved in asthma pathogenesis. We evaluated the effects of IL-9 blockade on chronic airway inflammation.
METHODS
Acute airway inflammation was induced in Balb/c mice using aerosolized ovalbumin (OVA), whereas chronic asthma was induced by OVA exposure for 5 weeks with anti-IL-9 or isotype-matched antibody (Ab) treatment during the OVA challenge. Inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted and lung tissues were stained to detect cellular infiltration, mucus deposition, and collagen accumulation. The levels of interferon (IFN)-gamma, IL-4, IL-5, IL-9, IL-17, and immunoglobulin E (IgE) in BALF were measured using enzyme linked immunosorbent assays, and profiles of inflammatory cells and subsets of T helper (Th) cells were analyzed using flow cytometry.
RESULTS
IL-9, IL-17, and IFN-gamma levels were significantly increased in the chronic group compared to the acute asthma group. However, the number of IL-9-positive cells was not affected, with a decrease in Th17 cells in OVA-challenged caspase-1 knockout mice. Numbers of eosinophils, neutrophils, B cells, mast cells, and Th17 cells decreased after administration of anti-IL-9 Ab. Total IgE, IL-5, IL-9, and IL-17 levels were also lower in the anti-IL-9 group.
CONCLUSIONS
Our results suggest that anti-IL-9 Ab treatment inhibits pulmonary infiltration of inflammatory cells and cytokine production, especially IL-17. These results provide a basis for the use of an anti-IL-9 Ab to combat IL-17-mediated airway inflammation.

Keyword

Interleukin-9; allergic asthma; T helper 17; anti-interleukin-9 antibody
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