title: IL-32, a novel proinflammatory cytokine in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Medical Diagnostic Sciences and Special Therapies, University of Padova, Padova, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Simonetta
authors.initials: S
authors.lastname: Baraldo
authors.forename: Erica
authors.initials: E
authors.lastname: Bazzan
authors.forename: Francesca
authors.initials: F
authors.lastname: Lunardi
authors.forename: Federico
authors.initials: F
authors.lastname: Rea
authors.forename: Piero
authors.initials: P
authors.lastname: Maestrelli
authors.forename: Graziella
authors.initials: G
authors.lastname: Turato
authors.forename: Kim
authors.initials: K
authors.lastname: Lokar-Oliani
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.forename: Renzo
authors.initials: R
authors.lastname: Zuin
authors.forename: Paolo
authors.initials: P
authors.lastname: Sfriso
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Balestro
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Marina
authors.initials: M
authors.lastname: Saetta
mesh_terms: D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000276:immunology; D007378:Interleukins / Q000097:blood* / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000503:physiopathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000276:immunology*; D012333:RNA, Messenger / Q000097:blood / Q000276:immunology; D012907:Smoking / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000097:blood / Q000276:immunology
chemical_list: D015415:Biomarkers; C496971:IL32 protein, human; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases