Interleukin-18-deficient mice exhibit diminished chronic inflammation and airway remodelling in ovalbumin-induced asthma model.
Interleukin (IL)-18, which is produced by activated monocytes/macrophages and airway epithelial cells, is suggested to contribute to the pathophysiology of asthma by modulating airway inflammation. However, the involvement of IL-18 on modulating chronic airway inflammation and airway remodelling, which are characterized in a refractory asthma model exposed to long-term antigen, has not been investigated sufficiently. We examined the role of IL-18 in chronic airway inflammation and airway remodelling by long-term antigen exposure. IL-18-deficient and C57BL/6-wild-type mice were sensitized by ovalbumin (OVA) and were then exposed to aerosolized OVA twice a week for 12 weeks. We assessed airway inflammation by assessing the infiltration of cells into the airspace and lung tissues, and airway remodelling by airway mucus expression, peribronchial fibrosis and smooth muscle thickness. In IL-18-deficient mice, when exposed to OVA, the total cells and neutrophils of the bronchoalveolar lavage fluid (BALF) were diminished, as were the number of infiltrated cells in the lung tissues. IL-18-deficient mice exposed to OVA after 12 weeks showed significantly decreased levels of interferon (IFN)-gamma, IL-13 and transforming growth factor (TGF)-beta1 in the BALF. The airway hyperresponsiveness to acetyl-beta-methacholine chloride was inhibited in IL-18-deficient mice in comparison with wild-type mice. In addition, IL-18-deficient mice exposed to OVA had fewer significant features of airway remodelling. These findings suggest that IL-18 may enhance chronic airway inflammation and airway remodelling through the production of IFN-gamma, IL-13 and TGF-beta1 in the OVA-induced asthma mouse model.
Yamagata
S
S
Department of Respiratory Medicine, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. yamagata@ko-arena.med.kindai.ac.jp
Tomita
K
K
Sato
R
R
Niwa
A
A
Higashino
H
H
Tohda
Y
Y
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D020382:Interleukin-18 / Q000172:deficiency* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology
D016207:Cytokines; D020382:Interleukin-18; D007073:Immunoglobulin E; D010047:Ovalbumin