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

Abstract

PurposeAsthma 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.MethodsAcute 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)-γ, 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.ResultsIL-9, IL-17, and IFN-γ 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.ConclusionsOur 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.

Interleukin-9 Is Associated with Elevated Anti-Double-Stranded DNA Antibodies in Lupus-Prone Mice

“…The animal protocol was approved by the Institutional Animal Use Committee of the Shanghai Institute for Biological Sciences. Some experiments were performed as modified methods (15,16). MRL/lpr mice were randomized into two groups containing six mice each and were treated with intraperitoneal (IP) injections of phosphate-buffered saline, anti-IL-9 antibody (100 μg/mouse), or anti-IL-19 antibody (100 μg/mouse) plus anti-IL-17 antibody (100 μg/mouse), (eBioscience, San Diego, CA, USA) once every 4 wks for 12 wks, and gremial center formation and kidney injury was analyzed.…”

Neurturin Influences Inflammatory Responses and Airway Remodeling in Different Mouse Asthma Models

“…These cells will then release matrix metalloproteinase-9 (MMP-9) involved in tissue remodeling (7). Many studies have explored therapeutic agents for asthma, nevertheless the variation in efficacy and possible side effects of these therapies determine a need for new treatments (8).…”

The impact of omega-3 fatty acids on lung histopathology in mice model of chronic asthma

“…Preliminary studies demonstrated almost always an increase in the numbers of neutrophils, eosinophils, macrophages and lymphocytes in the respiratory system of animals sensitized via OVA (Nabe et al, 2005;Nabe et al, 2011;Yang et al, 2011;Brandenberger et al, 2013;Kim et al, 2013). In this study, there was no difference between the two groups for eosinophilia and macrophage, with a slight difference in the number of lymphocytes (p=0.085).…”