INTERLEUKIN-11 INDUCES INTESTINAL EPITHELIAL-CELL GROWTH ARREST THROUGH EFFECTS ON RETINOBLASTOMA PROTEIN-PHOSPHORYLATION

Recombinant human (rh) interleukin (IL)-11 has been shown to reduce ga strointestinal mucosal injury after chemotherapy or irradiation in sev eral animal models. As reduction of cellular proliferation can be cyto protective, we have examined the effect of rhIL-11 compared with trans forming growth factor (TGF)-beta(1) on the proliferation and cell prog ression of a rat intestinal cell line, IEC-6. IEC-6 cells treated with rhIL-11 or rhTGF-beta(1) exhibited a reduced proliferative rate as me asured by cell counts and [H-3]thymidine incorporation. The presence o f neutralizing anti-TGF-beta(1) antibodies did not block the antiproli ferative effect of rhIL-11 indicating that the rhIL-11 activity was no t mediated through the induction of endogenous TGF-beta(1) production. Growth inhibition correlated with delayed entry into S phase of the c ell cycle. Cell cycle are was associated with suppression of retinobla stoma protein phosphorylation. Transient cell cycle arrest is a possib le mechanism by which rhIL-11 may protect intestinal epithelial cells from damage induced by chemotherapy or radiation therapy. This study p rovides a rationale for the clinical use of rhIL-11 to preserve the in tegrity of the gastrointestinal mucosa during cancer treatment regimen s.