RATIONALE: 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. OBJECTIVES: We investigated whether IL-32, a newly discovered cytokine, was related to markers of inflammation and clinical progression in COPD. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

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

CALABRESE, FIORELLA;BARALDO, SIMONETTA;BAZZAN, ERICA;LUNARDI, FRANCESCA;REA, FEDERICO;MAESTRELLI, PIERO;TURATO, GRAZIELLA;ZUIN, RENZO;SFRISO, PAOLO;BALESTRO, ELISABETTA;SAETTA, MARINA
2008

Abstract

RATIONALE: 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. OBJECTIVES: We investigated whether IL-32, a newly discovered cytokine, was related to markers of inflammation and clinical progression in COPD. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2438604
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