Abstract

BackgroundRadiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA) could ameliorate radiation-induced lung injury in mice.MethodsBALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1) or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA). Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline.ResultsThe mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control.ConclusionsOur findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

Highlights

  • Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy

  • Radiation pneumonia and/or pulmonary fibrosis occur in approximately 10-20% of patients treated with thoracic radiotherapy [1]

  • We examined the effect of anti-IL-6 monoclonal receptor antibody (IL-6RA) on radiation-induced lung injury in mice having received lethal irradiation of the whole thorax

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Summary

Introduction

Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA) could ameliorate radiation-induced lung injury in mice. An interstitial pulmonary inflammation, and subsequent radiation lung fibrosis are significant dose-limiting complications and may threaten quality of life for patients receiving radiation to the thorax. Radiation pneumonia and/or pulmonary fibrosis occur in approximately 10-20% of patients treated with thoracic radiotherapy [1]. At the cellular and tissue level, radiation pneumonia presents as an edema of the interstitial space, infiltration of inflammatory cells, and thickening of the alveolar septa. The molecular mechanism for radiation pneumonia is complex and obscure, involvement of proin-

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