IL-11, a pleiotropic cytokine: exciting new effects of IL-11 on gastrointestinal mucosal biology.
Recombinant human interleukin 11 (rhIL-11) is a pleiotropic cytokine that stimulates bone marrow stem cells to proliferate and decreases intestinal mucosal injury produced by cytoablative drugs and radiation in animals. The effects of rhIL-11 were studied in a hamster model of oral mucositis and in two rat models of inflammatory bowel disease (IBD). Oral mucositis was induced in male Golden Syrian hamsters with 5-fluorouracil 60 mg/kg intraperitoneal, days 0 and 2. Peak mucositis occurred by day 10 in vehicle treated animals. rhIL-11, given twice daily subcutaneously, decreased the mucositis in a dose-dependent manner and increased animal survival at all doses tested. In two models of IBD, the acetic acid-induced acute colonic injury model in Sprague-Dawley rats and the transgenic Fischer 344 rats expressing human HLA-B27 and beta 2-microglobulin, rhIL-11 decreased the gross and microscopic damage in the colons of these animals. These data suggest that rhIL-11 exerts effects on the gastrointestinal mucosa which ameliorate responses to injurious stimuli.
Keith
J C
JC
Genetics Institute, Inc., Cambridge, Massachusetts.
Albert
L
L
Sonis
S T
ST
Pfeiffer
C J
CJ
Schaub
R G
RG
D000085:Acetates / Q000633:toxicity; D019342:Acetic Acid; D000818:Animals; D030801:Animals, Genetically Modified; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D006224:Cricetinae; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D017370:Interleukin-11 / Q000494:pharmacology* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000293:injuries; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013280:Stomatitis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D001613:beta 2-Microglobulin / Q000235:genetics
D000085:Acetates; D015796:HLA-B27 Antigen; D017370:Interleukin-11; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D019342:Acetic Acid; D005472:Fluorouracil