The effect of steroids on radiation-induced lung disease in the rat.
We have used a model of bilateral radiation-induced lung disease in the rat to study the effects of corticosteroids. This model is characterized by interstitial edema at 2 weeks after radiotherapy followed by florid alveolitis with an alveolar protein leak which peaks at 4 weeks. Mast cell density peaks at 7 weeks, and there is a progressive increase in lung collagen (fibrosis) from 5 to 20 weeks. Intraperitoneal corticosteroids or saline were given at the time of irradiation or sham irradiation (protocol 1), every second day during weeks 3 and 4 (protocol 2), or three times weekly during weeks 3 to 8 (protocol 3). In protocol 1, steroids protected the lung from interstitial edema at 2 weeks, delayed the alveolitis without reducing its intensity, and significantly reduced the alveolar protein leak. However, radiation fibrosis was not reduced at 20 weeks. Longer steroid administration (protocol 2) suppressed the alveolar protein leak and delayed and significantly reduced the severity of the inflammatory cell response. Although the tissue mast cell and fibrotic responses were suppressed during and for at least 3 weeks after steroids, the ultimate fibrotic reaction was the same in both irradiated groups. In protocol 3, steroids suppressed the alveolitis and delayed the rise in tissue mast cell density, but did not affect the fibrotic response at 20 weeks. These studies suggest that steroids can suppress the alveolitis provided they are used throughout the period of alveolitis. Although they also delay the tissue mast cell response to radiation, the ultimate fibrosis is not altered. This provides further evidence for the dissociation of alveolitis and fibrosis after lung irradiation and has potential implications for management of radiation-induced lung disease in humans.
Ward
H E
HE
Department of Thoracic Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Kemsley
L
L
Davies
L
L
Holecek
M
M
Berend
N
N
D000818:Animals; D003094:Collagen / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000188:drug therapy; D017564:Radiation Pneumonitis / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D015430:Weight Gain / Q000187:drug effects / Q000528:radiation effects
D003094:Collagen; D008775:Methylprednisolone