Interleukin-17A antagonist attenuates radiation-induced lung injuries in mice.
OBJECTIVE
To investigate the effect of interleukin-17A (IL-17A) antibodies on radiation-induced lung injuries in mice.


METHODS
The thorax of 135 mice were divided into Sham (n = 30), radiation control (RC, n = 35), treatment (n = 35, IL-17A-neutralizing antibody, 4 μg/mouse, IV, 4 days per month for 4 months) and placebo group (n = 35) before a single dose irradiation (15 Gy) to the thorax. Inflammation and collagen contents in the lung tissues were examined, and the concentration of IL-17A, TGF-β1, and IL-6 in bronchoalveolar lavage fluid (BALF) were measured. In another 50 animals, 180-day survival rate following the irradiation and treatment was calculated by Kaplan-Meier method.


RESULTS
Sixteen weeks after the irradiation and treatment, there was significant inflammatory cell infiltration and interstitial collagen depositions in the radiation control and placebo groups, whereas these changes were relatively mild in the treatment group. The percentage of grade II and III alveolitis in the treatment group (16%, P < .05) was lower than in the RC (72%) or placebo group (64%). The mean Aschcroft fibrosis scores were 2.8 (treatment group), 5.2 (RC), and 4.8 (placebo group), respectively. The scores of treatment group was lower than that of RC (P < .001) or placebo group (P < .001). The IL-17A, TGF-β, and IL-6 concentrations in the treatment group were lower than in the RC and placebo group (P < .01) following the irradiation. The 180-day mortality rate in the treatment group was lower than in the RC group 16.7% versus 75.0%, P < .05).


CONCLUSIONS
IL-17A antibody treatment alleviates radiation-induced pneumonitis and subsequent fibrosis, and improvise postirradiation survival.
1Department of Oncology, Qilu Hospital, Shandong University, Jinan, P. R. China.
Bao-Zhong
BZ
Wang
Li-Ping
LP
Wang
Hui
H
Han
Fang-Li
FL
Cao
Guang-Yao
GY
Li
Jun-Long
JL
Xu
Xiu-Wen
XW
Wang
Le-Xin
LX
Wang
D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D055370:Lung Injury / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D015996:Survival Rate
D057134:Antibodies, Neutralizing; D016207:Cytokines; D020381:Interleukin-17; D003094:Collagen