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.

CONCLUSION:

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: Hanako Oda, Tomotaka Kawayama, Haruki Imaoka, Yuki Sakazaki, Yoichiro Kaku, Masaki Okamoto, Yasuhiko Kitasato, Nobutaka Edakuni, Shin-Ichi Takenaka, Makoto Yoshida, Tomoaki Iwanaga, Seiya Kato, Paul M O'Byrne, Tomoaki Hoshino
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 112 Issue 1 Pg. 23-28.e1 (Jan 2014) ISSN: 1534-4436 [Electronic] United States
• PMID: 24331389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-18
• Receptors, Interleukin-18

Topics

• Adolescent
• Adult
• Aged
• Asthma (immunology, mortality)
• Basophils (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Child, Preschool
• Eosinophils (immunology)
• Female
• Humans
• Interleukin-18 (biosynthesis)
• Leukocyte Count
• Lung (immunology)
• Macrophages (immunology)
• Male
• Middle Aged
• Neutrophils (immunology)
• Pneumonia (immunology)
• Receptors, Interleukin-18 (biosynthesis)
• Smoking
• Young Adult