IL-32, a novel proinflammatory cytokine in chronic obstructive pulmonary disease.
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.
Calabrese
Fiorella
F
Department of Medical Diagnostic Sciences and Special Therapies, University of Padova, Padova, Italy.
Baraldo
Simonetta
S
Bazzan
Erica
E
Lunardi
Francesca
F
Rea
Federico
F
Maestrelli
Piero
P
Turato
Graziella
G
Lokar-Oliani
Kim
K
Papi
Alberto
A
Zuin
Renzo
R
Sfriso
Paolo
P
Balestro
Elisabetta
E
Dinarello
Charles A
CA
Saetta
Marina
M
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
D015415:Biomarkers; C496971:IL32 protein, human; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases