Early administration of IL-6RA does not prevent radiation-induced lung injury in mice.
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.
Ogata
Toshiyuki
T
Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. ogata@radonc.med.osaka-u.ac.jp
Yamazaki
Hideya
H
Teshima
Teruki
T
Kihara
Ayaka
A
Suzumoto
Yuko
Y
Inoue
Takehiro
T
Nishimoto
Norihiro
N
Matsuura
Nariaki
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001835:Body Weight / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D006909:Hydroxyproline / Q000032:analysis; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D017564:Radiation Pneumonitis / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D000685:Serum Amyloid A Protein / Q000378:metabolism; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000685:Serum Amyloid A Protein; D006909:Hydroxyproline