title: Elevated plasma α-defensins in patients with acute exacerbation of fibrotic interstitial pneumonia.
abstract: BACKGROUND
  Patients with fibrosing interstitial lung diseases can develop acute exacerbation (AE). The aetiology of AE remains obscure, but neutrophils might play a pivotal role in the pathogenesis. Neutrophils store azurophil granules containing defensins that are antimicrobial peptides that also function in regulating the inflammatory response. The present study evaluates plasma levels of defensins in patients with AE of interstitial pneumonia (AE-IP) to determine their role(s) in the pathogenesis of AE-IP and whether defensins could serve as a biomarker of AE-IP.
  
  
  METHODS
  Plasma levels of defensins including human neutrophil peptides (HNPs) and human beta defensin 2 (HBD2) were measured using ELISA in 21 patients with AE-IP, 44 with stable (S)-IP, nine with IP complicated with pulmonary infection (Infec-IP), and in 23 healthy volunteers. Lung HNP expression was immunohistochemically analyzed in biopsy and autopsy tissues diagnosed as S-IP and AE-IP.
  
  
  RESULTS
  Plasma levels of HNPs were significantly higher in patients with AE-IP than with S-IP, but did not differ from those with Infec-IP and were not associated with other clinical features and prognosis. Plasma HNP were not specific in terms of distinguishing AE-IP from S-IP. Immunohistochemical analysis showed increased HNPs expression in accumulated neutrophils from patients with AE-IP. Plasma levels of HBD2 did not differ among patients with AE-IP, S-IP and Infec-IP.
  
  
  CONCLUSIONS
  Elevated plasma levels of HNPs were higher in AE-IP than in S-IP, but not specific enough to serve as candidate biomarkers of AE-IP. Further studies are needed to clarify the role of defensins in the pathogenesis of AE-IP.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Noriho
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishimatsu
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kakugawa
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yura
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Tomonaga
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Harada
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hara
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hara
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishimoto
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. Electronic address: hmukae@med.uoeh-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D023084:alpha-Defensins / Q000097:blood*
chemical_list: D015415:Biomarkers; D023084:alpha-Defensins
keywords: Human neutrophil peptide; Idiopathic pulmonary fibrosis; Interstitial lung disease; Microbial peptide