Association of elevated alpha-defensin levels with interstitial pneumonia in patients with systemic sclerosis

作者：Sakamoto Noriho^*; Kakugawa Tomoyuki; Hara Atsuko; Nakashima Shota; Yura Hirokazu; Harada Tatsuhiko; Ishimoto Hiroshi; Yatera Kazuhiro; Kuwatsuka Yutaka; Hara Toshihide; Ichinose Kunihiro; Obase Yasushi; Ishimatsu Yuji; Kohno Shigeru; Mukae Hiroshi

来源：Respiratory Research, 2015, 16(1): 148.

DOI：10.1186/s12931-015-0308-1

• Bronchoalveolar lavage fluid
• Human neutrophil peptide
• Interleukin-8
• Interstitial lung disease

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.

• 出版日期2015-12-10