title: Interleukin-18 expression, CD8(+) T cells, and eosinophils in lungs of nonsmokers with fatal asthma.
abstract: BACKGROUND
  The process of airway inflammation in the lungs of nonsmokers who die of asthma (fatal asthma) has not been reported in detail.
  
  
  OBJECTIVE
  To examine nonsmokers who had died of asthma to exclude chronic obstructive pulmonary disease and investigate pulmonary inflammatory cells and the expression of interleukin-18 (IL-18) and its receptor in lung tissues compared with those in patients with well-controlled mild asthma and nonsmokers.
  
  
  METHODS
  Lung tissues were obtained at autopsy examination from 12 nonsmokers with fatal asthma, excluding cases of chronic obstructive pulmonary disease, and from 5 nonsmokers with well-controlled mild asthma and 10 nonsmokers who had undergone surgical resection for lung cancer. Pulmonary inflammatory cells were examined and the expression of the proinflammatory cytokine IL-18 and its receptor in the lungs was evaluated.
  
  
  RESULTS
  The numbers of eosinophils and lymphocytes, but not basophils or macrophages, were significantly increased in the lungs of patients with fatal asthma compared with the other 2 groups. The lung neutrophil count did not differ significantly between the fatal and mild asthma groups but was significantly higher in the fatal asthma group than in nonsmokers. CD8(+) T cells, but not CD4(+) T cells, were significantly increased in the lungs of the fatal asthma group compared with the other 2 groups. IL-18 protein and IL-18 receptor were strongly expressed in the lungs in the fatal asthma group.
  
  
  CONCLUSIONS
  Caspase-1 inhibitors, anti-IL-18 antibodies, anti-IL-18 receptor antibodies, IL-18 binding protein, or inhibitors of genes downstream of the IL-18 signal transduction pathway may be of clinical benefit for the treatment of patients with severe asthma.
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors: Hanako
authors: H
authors: Oda
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors: Tomotaka
authors: T
authors: Kawayama
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors: Haruki
authors: H
authors: Imaoka
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors: Yuki
authors: Y
authors: Sakazaki
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors: Yoichiro
authors: Y
authors: Kaku
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors: Masaki
authors: M
authors: Okamoto
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors: Yasuhiko
authors: Y
authors: Kitasato
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors: Nobutaka
authors: N
authors: Edakuni
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors: Shin-Ichi
authors: S
authors: Takenaka
authors: Fukuoka National Hospital, Fukuoka, Japan.
authors: Makoto
authors: M
authors: Yoshida
authors: Fukuoka National Hospital, Fukuoka, Japan.
authors: Tomoaki
authors: T
authors: Iwanaga
authors: Division of Pathology and Cell Biology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
authors: Seiya
authors: S
authors: Kato
authors: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Paul M
authors: PM
authors: O'Byrne
authors: Division of Respirology, Neurology, and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Kurume, Japan. Electronic address: hoshino@med.kurume-u.ac.jp.
authors: Tomoaki
authors: T
authors: Hoshino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology* / Q000401:mortality; D001491:Basophils / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002675:Child, Preschool; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology; D053724:Receptors, Interleukin-18 / Q000096:biosynthesis; D012907:Smoking; D055815:Young Adult
chemical_list: D020382:Interleukin-18; D053724:Receptors, Interleukin-18