title: Association of elevated α-defensin levels with interstitial pneumonia in patients with systemic sclerosis.
abstract: BACKGROUND
  Interstitial lung disease (ILD) is the leading cause of mortality in patients with systemic sclerosis (SSc). Although the pathogenesis of SSc-ILD is not well understood, neutrophils may play a pivotal role in this process. Neutrophils store azurophil granules that contain defensins, antimicrobial peptides that function in regulating the inflammatory response, and IL-8, a potent chemoattractant for neutrophils. The present study evaluated the levels of defensins and IL-8 in patients with SSc-ILD to determine their roles in disease pathogenesis.
  
  
  METHODS
  Defensins (also known as human neutrophil peptides, HNPs) and IL-8 levels were measured in the serum and bronchoalveolar lavage fluid (BALF) of 33 patients with SSc-ILD and in 20 healthy controls by using ELISA.
  
  
  RESULTS
  BALF analysis revealed a significant increase in HNPs in SSc-ILD patients (median; 240.0 pg/mL) than that of healthy controls (79.7 pg/mL). Additionally, IL-8 levels were higher in SSc-ILD patient serum and BALF as compared to healthy controls (16.4 pg/mL vs. 5.8 pg/mL and 15.4 pg/mL vs. 14.5 pg/mL, respectively). However, plasma HNPs levels were relatively unchanged. HNP and IL-8 levels in patient BALF displayed a significant positive correlation significantly correlated (r = 0.774, p <0.01), and which also correlated with clinical disease parameters--such as ILD biomarkers, pulmonary function tests, ratio of neutrophils and eosinophils in BALF, tricuspid regurgitation peak gradient (TRPG), and the extent of high-resolution computed tomography (HRCT) findings in the lung. Levels of plasma HNPs and serum IL-8 did not show a significant correlation with any clinical parameter. SSc-ILD progression was evaluated by pulmonary function tests, but no association was observed between VC change ratios and HNPs or IL-8 levels.
  
  
  CONCLUSIONS
  BALF levels of HNPs and IL-8 were higher in SSc-ILD than in healthy controls, and are associated with various clinical disease parameters. Further studies are needed to clarify the role of defensins and IL-8 in SSc-ILD pathogenesis.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. nsakamot@nagasaki-u.ac.jp.
authors.forename: Noriho
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. kakugawa@nagasaki-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kakugawa
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. a-hara@nagasaki-u.ac.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hara
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. shonaka@nagasaki-u.ac.jp.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. h_yura.5994@me.com.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yura
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. harada-nagasaki@umin.ac.jp.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. h-ishimoto@med.uoeh-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishimoto
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. yatera@med.uoeh-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Nagasaki University, Nagasaki, Japan. y-kuwa83@nagasaki-u.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kuwatsuka
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Nagasaki University, Nagasaki, Japan. t-hara@nagasaki-u.ac.jp.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. kichinos@nagasaki-u.ac.jp.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ichinose
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. obaseya@nagasaki-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Obase
authors.affiliation: Department of Cardiopulmonary Rehabilitation Science, Unit of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. yuji-i@nagasaki-u.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishimatsu
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. s-kohno@nagasaki-u.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. hmukae@nagasaki-u.ac.jp.|Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. hmukae@nagasaki-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D017563:Lung Diseases, Interstitial / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000097:blood* / Q000175:diagnosis; D012720:Severity of Illness Index; D015854:Up-Regulation; D023084:alpha-Defensins / Q000097:blood*
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D016209:Interleukin-8; D023084:alpha-Defensins