Transforming growth factor (TGF)-β has been implicated in any fibrotic conditions. However, its mechanistic role in radiation toxicity is equivocal despite compelling correlative evidence. This study assessed whether in vivo administration of a soluble TGF-β type II receptor (TβR-II) protein ameliorates intestinal radiation injury (radiation enteropathy).

A recombinant fusion protein, consisting of the extracellular portion of mouse TβR-II and the Fc portion of mouse immunoglobulin (Ig) G, was produced. A 5-cm segment of mouse ileum was exposed to 19 Gy x-radiation. TβR-II:Fc fusion protein (1 mg/kg every other day) or mouse IgG was administered from 2 days before to 6 weeks after irradiation. Radiation injury was assessed at 6 weeks using quantitative histology, morphometry, and immunohistochemistry. Collagen was measured colorimetrically, and TGF-β1 messenger RNA was assessed with fluorogenic probe reverse-transcription polymerase chain reaction.

Compared with IgG controls, TβR-II:Fc-treated mice exhibited less structural injury, preservation of mucosal surface area, and less intestinal wall fibrosis. Intestinal TGF-β1 messenger RNA increased in TβR-II:Fc-treated mice, whereas TGF-β immunoreactivity decreased. TβR-II:Fc treatment increased crypt cell proliferation but otherwise did not affect unirradiated intestine.

Long-term modulation of TGF-β with a TβR-II:Fc fusion protein is feasible and ameliorates radiation enteropathy. These data confirm the putative role of TGF-β in intestinal radiation fibrosis.