IL-32, a Novel Proinflammatory Cytokine in Chronic Obstructive Pulmonary Disease

• Published in: American journal of respiratory and critical care medicine 2008-11, Vol.178 (9), p.894-901
• Main Authors: Calabrese, Fiorella, Baraldo, Simonetta, Bazzan, Erica, Lunardi, Francesca, Rea, Federico, Maestrelli, Piero, Turato, Graziella, Lokar-Oliani, Kim, Papi, Alberto, Zuin, Renzo, Sfriso, Paolo, Balestro, Elisabetta, Dinarello, Charles A, Saetta, Marina
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Asymptomatic; Biological and medical sciences; Biomarkers - blood; CD8-Positive T-Lymphocytes - immunology; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; Cytokines; Female; Humans; Inflammation - blood; Inflammation - etiology; Inflammation - immunology; Intensive care medicine; Interleukins - blood; Interleukins - immunology; Kinases; Lung - immunology; Lung - physiopathology; Lung - surgery; Lung diseases; Lymphocytes; Male; Medical sciences; Microscopy; Middle Aged; Neutrophils; p38 Mitogen-Activated Protein Kinases - blood; p38 Mitogen-Activated Protein Kinases - immunology; Pneumology; Pneumonia; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - immunology; Rheumatoid arthritis; RNA, Messenger - blood; RNA, Messenger - immunology; Smoking - adverse effects; Surgery; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-TNF
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200804-646OC

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung, yet the mechanisms that regulate this immune-inflammatory response are not fully understood. We investigated whether IL-32, a newly discovered cytokine, was related to markers of inflammation and clinical progression in COPD. Using immunohistochemistry, expression of IL-32 was examined in surgically resected specimens from 40 smokers with COPD (FEV(1) = 39 +/- 4% predicted), 11 smokers with normal lung function, and 9 nonsmoking control subjects. IL-32 was quantified in alveolar macrophages, alveolar walls, bronchioles, and arterioles, and confirmed by molecular analysis. The levels of IL-32 were correlated with the cellular infiltrates, markers of inflammation, and clinical data. Macrophage staining for IL-32 was increased in smokers with COPD compared with control smokers and nonsmokers (P = 0.0014 and P < 0.0001, respectively), and similar differences were observed in alveolar walls (P = 0.0004 and P = 0.0005) and bronchiolar epithelium (P = 0.004 and P = 0.0009). This increase was also detected at the mRNA level (P = 0.007 vs. control smokers and P = 0.029 vs. nonsmokers) and was mainly due to non-alpha isoforms. Moreover, IL-32 expression was positively correlated with tumor necrosis factor-alpha (P = 0.004, r(s)=0.70), CD8(+)cells (P = 0.02, r(s)=0.46), phospho p38MAPK (P < 0.01, r(s)=0.60) and negatively with FEV(1) values (P = 0.004, r(s)= -0.53). This is the first study to demonstrate increased expression of IL-32 in lung tissue of patients with COPD, where it was colocalized with tumor necrosis factor-alpha and correlated with the degree of airflow obstruction. These results suggest that IL-32 is implicated in the characteristic immune response of COPD, with a possible impact on disease progression.