Elevated plasma α-defensins in patients with acute exacerbation of fibrotic interstitial pneumonia

Noriho Sakamoto， Yuji Ishimatsu， Tomoyuki Kakugawa， Hirokazu Yura， Masaomi Tomonaga， Tatsuhiko Harada， Shota Nakashima， Shintaro Hara， Atsuko Hara， Hiroshi Ishimoto， Kazuhiro Yatera， Hiroshi Mukaee， Shigeru Kohno

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.

respiratory medicine

February 2015Volume 109, Issue 2, Pages 265–271

DOI: http://dx.doi.org/10.1016/j.rmed.2014.12.015 |