Recombinant human interleukin-11 restores smooth muscle function in the jejunum and colon of human leukocyte antigen-B27 rats with intestinal inflammation.
Recombinant human interleukin (rhIL)-11 has anti-inflammatory and protective effects in models of intestinal mucosal injury. Our aim was to investigate whether oral treatment with rhIL-11 reverses functional abnormalities in intestinal muscle contractility resulting from human leukocyte antigen (HLA)-B27-dependent gut inflammation. Isometric contractions were studied in jejunal and colonic longitudinal muscles. Muscle strips were isolated from HLA-B27 transgenic rats with spontaneous inflammation following treatment with enteric-coated rhIL-11 multiparticulates (500 microg/kg) or placebo multiparticulates given orally every 48 h for 2 weeks. Myeloperoxidase (MPO) activity was measured in intestinal tissue samples and served as an index of inflammation. Colonic damage was also assessed histologically. The HLA-B27 rats receiving placebo had chronic diarrhea, and MPO activity was increased in the jejunum and colon. Intestinal inflammation was associated with a decreased ability of the muscles to generate active tension in response to electrical field stimulation, carbachol, or high KCl. In the jejunum of placebo-treated HLA-B27 rats, concentration-effect curves for carbachol were shifted to lower concentrations yielding a higher EC50. Oral treatment of HLA-B27 rats with rhIL-11 suppressed the symptoms of diarrhea, normalized MPO activity, and improved the colonic damage score. Simultaneously, neurally mediated responses were improved and the maximal tension generated by carbachol or KCl was normalized in the jejunum and colon. The EC50 for carbachol in the jejunum of HLA-B27 rats was also normalized by rhIL-11 treatment. Our data demonstrate that oral administration of enteric-coated rhIL-11 suppresses intestinal inflammation and reverses intestinal smooth muscle dysfunction in HLA-B27 transgenic rats.
Greenwood-Van Meerveld
B
B
Oklahoma Foundation for Digestive Research Basic Science Laboratories, Veterans Affairs Medical Center, Oklahoma City, Oklahoma 73104, USA. Beverley-Greenwood@ouhsc.edu
Venkova
K
K
Keith
J C
JC
D000818:Animals; D003106:Colon / Q000473:pathology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004751:Enteritis / Q000473:pathology* / Q000503:physiopathology*; D005243:Feces; D015796:HLA-B27 Antigen / Q000235:genetics*; D017370:Interleukin-11 / Q000494:pharmacology*; D007583:Jejunum / Q000473:pathology / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology
D015796:HLA-B27 Antigen; D017370:Interleukin-11; D011994:Recombinant Proteins; D009195:Peroxidase