Interleukin-18 production and pulmonary function in COPD.
Interleukin (IL)-18 production and pulmonary function were evaluated in patients with chronic obstructive pulmonary disease (COPD) in order to determine the role of IL-18 in COPD. Immunohistochemical techniques were used to examine IL-18 production in the lungs of patients with very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV, n = 16), smokers (n = 27) and nonsmokers (n = 23). Serum cytokine levels and pulmonary function were analysed in patients with GOLD stage I-IV COPD (n = 62), smokers (n = 34) and nonsmokers (n = 47). Persistent and severe small airway inflammation was observed in the lungs of ex-smokers with very severe COPD. IL-18 proteins were strongly expressed in alveolar macrophages, CD8+ T-cells, and both the bronchiolar and alveolar epithelia in the lungs of COPD patients. Serum levels of IL-18 in COPD patients and smokers were significantly higher than those in nonsmokers. Moreover, serum levels of IL-18 in patients with GOLD stage III and IV COPD were significantly higher than in smokers and nonsmokers. There was a significant negative correlation between serum IL-18 level and the predicted forced expiratory volume in one second in patients with COPD. In contrast, serum levels of IL-4, IL-13 and interferon-gamma were not significantly increased in any of the three groups. In conclusion, overproduction of interleukin-18 in the lungs may be involved in the pathogenesis of chronic obstructive pulmonary disease.
Imaoka
H
H
Division of Respirology, Neurology and Rheumatology, Dept of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Hoshino
T
T
Takei
S
S
Kinoshita
T
T
Okamoto
M
M
Kawayama
T
T
Kato
S
S
Iwasaki
H
H
Watanabe
K
K
Aizawa
H
H
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000401:mortality* / Q000473:pathology* / Q000503:physiopathology; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis
D015415:Biomarkers; D018793:Interleukin-13; D020382:Interleukin-18; D007371:Interferon-gamma