Anti-interleukin-33 inhibits cigarette smoke-induced lung inflammation in mice.
The mechanism by which cigarette smoke (CS) causes chronic obstructive pulmonary disease (COPD) is poorly understood. Interleukin-33 (IL-33) is a pleiotropic cytokine predominantly expressed in lung tissue and can elicit airway inflammation in naive mice. We tested the hypothesis that IL-33 is induced by CS and contributes to CS-mediated airway inflammation in a mouse model of CS-induced COPD. Groups of mice were exposed to CS three times per day for 4 consecutive days. The expression levels of IL-33 and ST2 were markedly enhanced in the lung tissue of mice inhaling CS. Exposure to CS also induced neutrophil and macrophage infiltration and expression of inflammatory cytokines (IL-1β, tumour necrosis factor-α, IL-17), chemokines (monocyte chemoattractant protein-1) and mucin 5, subtypes A and C in the airways. More importantly, all of these CS-induced pathogenic changes were significantly inhibited by treatment with neutralizing anti-IL-33 antibody delivered intranasally. Hence, our results suggest that IL-33 plays a critical role in CS-mediated airway inflammation and may be a therapeutic target in CS-related diseases, including COPD.
Department of Immunology, Medical School of Ningbo University, Ningbo, China.
Chuan
C
Qiu
Yan
Y
Li
Mingcai
M
Li
Min
M
Li
Xiaojin
X
Liu
Charles
C
McSharry
Damo
D
Xu
D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D000067596:Interleukin-33; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D012907:Smoking / Q000009:adverse effects*
D000906:Antibodies; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins