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Early administration of IL-6RA does not prevent radiation-induced lung injury in mice.

Ogata T, Yamazaki H, Teshima T, Kihara A, Suzumoto Y, Inoue T, Nishimoto N, Matsuura N - Radiat Oncol (2010)

Bottom Line: Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation.Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA).Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. ogata@radonc.med.osaka-u.ac.jp

ABSTRACT

Background: 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.

Methods: BALB/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.

Results: The 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.

Conclusions: Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

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Effects of IL-6RA treatment on radiation-induced lung injury indices. (A) Lung weight after 21 Gy of single irradiation to whole thorax with (white square) or without (black square) IL-6RA treatment. (B) Hydroxyproline levels in lung homogenates obtained from IL-6RA injected mice (white square) or control (black square). Data obtained from 5 animals in each group are presented as means ± SD. Dotted line shows each from mean value of non-irradiated mice + SD to mean value of them -SD.
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Figure 3: Effects of IL-6RA treatment on radiation-induced lung injury indices. (A) Lung weight after 21 Gy of single irradiation to whole thorax with (white square) or without (black square) IL-6RA treatment. (B) Hydroxyproline levels in lung homogenates obtained from IL-6RA injected mice (white square) or control (black square). Data obtained from 5 animals in each group are presented as means ± SD. Dotted line shows each from mean value of non-irradiated mice + SD to mean value of them -SD.

Mentions: Lung weight was measured to assess pulmonary edema and consolidation (Figure 3A) and after lung irradiation a gradual, time-dependent increase in lung weight was observed in the IL-6RA group as compared with the control group. However, the difference in lung weight between the two groups did not become significant at any time after irradiation.


Early administration of IL-6RA does not prevent radiation-induced lung injury in mice.

Ogata T, Yamazaki H, Teshima T, Kihara A, Suzumoto Y, Inoue T, Nishimoto N, Matsuura N - Radiat Oncol (2010)

Effects of IL-6RA treatment on radiation-induced lung injury indices. (A) Lung weight after 21 Gy of single irradiation to whole thorax with (white square) or without (black square) IL-6RA treatment. (B) Hydroxyproline levels in lung homogenates obtained from IL-6RA injected mice (white square) or control (black square). Data obtained from 5 animals in each group are presented as means ± SD. Dotted line shows each from mean value of non-irradiated mice + SD to mean value of them -SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2864283&req=5

Figure 3: Effects of IL-6RA treatment on radiation-induced lung injury indices. (A) Lung weight after 21 Gy of single irradiation to whole thorax with (white square) or without (black square) IL-6RA treatment. (B) Hydroxyproline levels in lung homogenates obtained from IL-6RA injected mice (white square) or control (black square). Data obtained from 5 animals in each group are presented as means ± SD. Dotted line shows each from mean value of non-irradiated mice + SD to mean value of them -SD.
Mentions: Lung weight was measured to assess pulmonary edema and consolidation (Figure 3A) and after lung irradiation a gradual, time-dependent increase in lung weight was observed in the IL-6RA group as compared with the control group. However, the difference in lung weight between the two groups did not become significant at any time after irradiation.

Bottom Line: Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation.Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA).Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. ogata@radonc.med.osaka-u.ac.jp

ABSTRACT

Background: 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.

Methods: BALB/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.

Results: The 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.

Conclusions: Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

Show MeSH
Related in: MedlinePlus