Abstract
BackgroundInterstitial 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.MethodsDefensins (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.ResultsBALF 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.ConclusionsBALF 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.
Highlights
Interstitial lung disease (ILD) is the leading cause of mortality in patients with systemic sclerosis (SSc)
Serum, and bronchoalveolar lavage fluid (BALF) levels of human neutrophil peptides (HNP) and IL-8 HNP analysis revealed significantly higher levels in the BALF of SSc-ILD patients than that of healthy controls (79.7 pg/ mL, 65.6–107.8 pg/mL, p
In the present study, we found elevated levels of BALF HNPs, BALF IL-8, and serum IL-8 in SSc-ILD patients when compared with healthy controls, but no significant differences were observed with respect to plasma HNPs
Summary
Interstitial lung disease (ILD) is the leading cause of mortality in patients with systemic sclerosis (SSc). The present study evaluated the levels of defensins and IL-8 in patients with SSc-ILD to determine their roles in disease pathogenesis. Pulmonary involvement is prominent in SSc, and interstitial lung disease (ILD) is the leading cause of mortality in SSc patients [2]. SSc-ILD pathogenesis is not well understood, the aberrant function of a variety of lung cells, cytokines, growth factors, peptides, and bioactive proteins, in combination with genetic and epigenetic regulators, have crucial functions in this process [3]. The extent of disease observed with HRCT and lower diffusing capacity of carbon monoxide (DLco) are reported to be associated with poor SSc-ILD prognosis [5, 6]. The cellular analysis of bronchoalveolar lavage fluid (BALF) is limited to excluding infection [4], it has been reported that neutrophilia in BALF is associated with disease severity [7]
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