The Role of Interleukin-32 in the Pathogenesis and Exacerbation of Bronchial Asthma

Abstract

Background Innate immunity and infection are important in the development and exacerbation of asthma. Interleukin-32 (IL-32), a pro-inflammatory cytokine involved with innate immunity against various infectious stimuli, is involved in various chronic inflammatory diseases such as rheumatoid arthritis, Crohns disease, and chronic obstructive pulmonary disease (COPD). This study was conducted to evaluate the role of IL-32 in asthma. Methods The role of IL-32γ in the airway was investigated in human bronchial epithelial cells (BEAS2B) stimulated with common asthma aggravating factors such as NOD ligands, dsRNA, lipopolysaccharide (LPS), and allergen (Der p) from house dust mites. IL-32γ was measured in the plasma of patients with asthma (n = 103) and healthy controls (n = 51), and then determined in induced sputum supernatant of patients with asthma (n = 89). Relationships between IL-32γ, airway obstruction (FEV1), inflammation (neutrophil and eosinophil % of the airway) and exacerbation frequency were evaluated. Results In in vitro study, IL-32γ exhibited synergistic effects with NOD 1 ligand and dsRNA on the induction of IL-6 from BEAS2B cells, but not by LPS and Der p. Plasma IL-32γ was detected in 95% (98/103) of patients with asthma and the level of IL-32γ was higher in asthmatic patients than in healthy controls. In the analysis of induced sputum, IL-32γ was detected in the sputum of 25 of 89 (28.1%) patients with asthma, and the asthma exacerbation rate was significantly higher in this group (n = 25) than in the IL-32-negative group (n = 64) (p = 0.03). Conclusion This study suggests that IL-32γ in the airway could increase inflammatory response to infectious stimuli and there could be an important role of IL-32 in subtype of asthma characterized by frequent exacerbations.