Anti‐interleukin‐33 inhibits cigarette smoke‐induced lung inflammation in mice

Abstract

SummaryThe 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-1b, tumour necrosis factor-a, 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 CSrelated diseases, including COPD.

Exacerbating Factors Induce Different Gene Expression Profiles in Peripheral Blood Mononuclear Cells from Asthmatics, Patients with Chronic Obstructive Pulmonary Disease and Healthy Subjects

“…A recent study using a mouse model showed that the expression levels of IL-33 and ST2 were markedly enhanced in the lung tissue after inhalation of cigarette smoke [61]. This observation supports those presented by Hacker et al [62], who reported increased serum levels of soluble ST-2 in COPD patients compared with healthy controls.…”

Targeting IL-33 in Autoimmunity and Inflammation

“…Intranasal anti-IL-33 antibody significantly inhibited cigarette smoke-induced lung inflammation in mice, as evidenced by reduced levels of IL-33 and ST2, as well as decreased number of neutrophil and macrophage infiltration along with decreased expression of inflammatory cytokines (IL-1b, TNF, IL-17) (Qiu et al, 2013). Mice challenged with ovalbumin and then treated with anti-IL-33 antibody or sST2 showed negative regulation of ovalbumin-induced allergic airway inflammation (Lee et al, 2014); both treatments decreased Th2 cytokine levels in bronchoalveolar lavage fluid and decreased the count of eosinophils (Lee et al, 2014).…”

Expression of interleukin-33 is correlated with poor prognosis of patients with squamous cell carcinoma of the tongue

“…Inflammation mediated by tobacco smoking, which is associated with tongue SCC, induces the expression of IL-33/ST2 in mice [25]. In the present study, we determined the expression of IL-33 in patients with tongue SCC using immunohistochemistry and assessed the relationship between the expression of IL-33 and prognosis of tongue SCC.…”