title: The progression of comorbidity in IL-18 transgenic chronic obstructive pulmonary disease mice model.
abstract: Patients with severe COPD are known to have comorbidities such as emaciation, cor pulmonale and right heart failure, muscle weakness, hyperlipemia, diabetes mellitus, osteoporosis, muscle atrophy, arterial sclerosis, hypertension, and depression. Therefore, treatment for COPD needs to focus on these comorbidities as well as the lungs. We previously reported a new mouse model of COPD utilizing the human surfactant protein C promoter SP-C to drive the expression of mature mouse IL-18 cDNA; constitutive IL-18 overproduction in the lungs of transgenic (Tg) mice induces severe emphysematous change, dilatation of the right ventricle, and mild pulmonary hypertension with aging. In the present study, we evaluated the progression of comorbidity in our COPD model. In female Tg mice, significant weight loss was observed at 16 weeks and beyond, when compared with control wild-type (WT) mice. This weight loss was suppressed in IL-13-deficient (knockout; KO) Tg mice. Muscle weight and bone mineral density were significantly decreased in aged Tg mice relative to control WT and IL-13 KO Tg mice. The aged Tg mice also showed impaired glucose tolerance. IL-18 and IL-13 may play important roles in the pathogenesis of comorbidity in COPD patients.
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Takenaka
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Kawayama
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Imaoka
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sakazaki
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Hanako
authors.initials: H
authors.lastname: Oda
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kaku
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Matsuoka
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Division of Pathology and Cell Biology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Kato
authors.affiliation: Division of Endocrinology and Metabolism, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. Electronic address: hoshino@med.kurume-u.ac.jp.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
mesh_terms: D000375:Aging; D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D015897:Comorbidity; D004195:Disease Models, Animal; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D015431:Weight Loss
chemical_list: D018793:Interleukin-13; D020382:Interleukin-18
keywords: COPD; IL-13; IL-18; Transgenic mouse