The soluble tumor necrosis factor-alpha receptor suppresses airway inflammation in a murine model of acute asthma

Yonsei Med J. 2009 Aug 31;50(4):569-75. doi: 10.3349/ymj.2009.50.4.569. Epub 2009 Aug 19.

Abstract

Purpose: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. TNF-alpha blocking strategies are now being tried in asthma patients. This study investigated whether TNF-alpha blocking therapy inhibits airway inflammation and airway hyperresponsiveness (AHR) in a mouse model of asthma. We also evaluated the effect of TNF-alpha blocking therapy on cytokine production and adhesion molecule expression.

Materials and methods: Ovalbumin (OVA) sensitized BALB/c female mice were exposed to intranasal OVA administration on days 31, 33, 35, and 37. Mice were treated intraperitoneally with soluble TNF-alpha receptor (sTNFR) during the OVA challenge.

Results: There were statistically significant decreases in the numbers of total cell and eosinophil in bronchoalveolar lavage fluid (BALF) in the sTNFR treated group compared with the OVA group. However, sTNFR-treatment did not significantly decrease AHR. Anti-inflammatory effect of sTNFR was accompanied with reduction of T helper 2 cytokine levels including interleukin (IL)-4, IL-5 and IL-13 in BALF and vascular cell adhesion molecule 1 expression in lung tissue.

Conclusion: These results suggest that sTNFR treatment can suppress the airway inflammation via regulation of Th2 cytokine production and adhesion molecule expression in bronchial asthma.

Keywords: Asthma; airway inflammation; soluble TNF-α receptor.

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / immunology*
  • Blotting, Western
  • Bronchi / drug effects
  • Bronchial Hyperreactivity
  • Bronchoalveolar Lavage Fluid / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunohistochemistry
  • Inflammation / drug therapy*
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / pharmacology
  • Tumor Necrosis Factor-alpha / therapeutic use*

Substances

  • Anti-Asthmatic Agents
  • Interleukin-13
  • Interleukin-5
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Ovalbumin