A bone marrow stromal-derived growth factor, interleukin-11, stimulates recovery of small intestinal mucosal cells after cytoablative therapy.
The proliferation of epithelial cells lining the small intestinal mucosa may be regulated by microenvironmental signals leading to differentiation of precursor cells in the small intestinal crypts. Proliferation of hematopoietic cells within the hematopoietic microenvironment is known to be regulated by a growing number of glycoprotein growth factors in a hierarchial fashion. We studied the effects of administration of the microenvironment-derived hematopoietic growth factor interleukin-11 (IL-11) on mice given combination radiation/chemotherapy. Treatment of such mice with IL-11 led to significantly increased survival and evidence of rapid recovery of the small intestinal mucosa, which is severely damaged by these cytoxic agents. This recovery was associated with an increase in the mitotic index of crypt cells and an increased frequency of staining of these cells with a monoclonal antibody to proliferating cell nuclear antigen, a member of the cyclin family of nuclear antigens.
Du
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Herman B. Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children, Indianapolis, IN.
Doerschuk
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CM
Orazi
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Williams
D A
DA
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D005472:Fluorouracil / Q000633:toxicity; D017370:Interleukin-11 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D017154:Stromal Cells / Q000737:chemistry
D017370:Interleukin-11; D005472:Fluorouracil