Masaki Tominaga1, Masaki Okamoto2, Tomotaka Kawayama3, Masanobu Matsuoka4, Shinjiro Kaieda5, Yuki Sakazaki6, Takashi Kinoshita7, Daisuke Mori8, Akira Inoue9, Tomoaki Hoshino10. 1. Department of Medicine 1, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume 830-0011, Japan. Electronic address: tominaga_masaki@med.kurume-u.ac.jp. 2. Department of Medicine 1, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume 830-0011, Japan. Electronic address: okamoto_masaki@med.kurume-u.ac.jp. 3. Department of Medicine 1, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume 830-0011, Japan. Electronic address: kawayama_tomotaka@med.kurume-u.ac.jp. 4. Department of Medicine 1, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume 830-0011, Japan. Electronic address: matsuoka_masanobu@kurume-u.ac.jp. 5. Department of Medicine 1, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume 830-0011, Japan. Electronic address: kaieda@med.kurume-u.ac.jp. 6. Department of Medicine 1, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume 830-0011, Japan. Electronic address: sakazaki@med.kurume-u.ac.jp. 7. Department of Medicine 1, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume 830-0011, Japan. Electronic address: tkino@kurume-u.ac.jp. 8. Department of Pathology, Saga-Ken Medical Centre Koseikan, Kase 400, Saga 840-8571, Japan. Electronic address: mori-d@koseikan.jp. 9. Department of Respiratory, Tohoku University, Aobaku, Sendai 980-8575, Japan. Electronic address: akinoue@idac.tohoku.ac.jp. 10. Department of Medicine 1, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume 830-0011, Japan; CIP, NCI-Frederick, NIH, Frederick, MD 21702, United States. Electronic address: hoshino@med.kurume-u.ac.jp.
Abstract
BACKGROUND: Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. METHODS: To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. RESULTS: IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. CONCLUSIONS: IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF.
BACKGROUND:Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. METHODS: To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-humanIL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancerpatients who underwent extirpation surgery. RESULTS:IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. CONCLUSIONS:IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF.
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