PMID- 11561063
OWN - NLM
STAT- MEDLINE
DCOM- 20011018
LR  - 20061115
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 299
IP  - 1
DP  - 2001 Oct
TI  - Recombinant human interleukin-11 restores smooth muscle function in the jejunum 
      and colon of human leukocyte antigen-B27 rats with intestinal inflammation.
PG  - 58-66
AB  - 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.
FAU - Greenwood-Van Meerveld, B
AU  - Greenwood-Van Meerveld B
AD  - Oklahoma Foundation for Digestive Research Basic Science Laboratories, Veterans 
      Affairs Medical Center, Oklahoma City, Oklahoma 73104, USA. 
      Beverley-Greenwood@ouhsc.edu
FAU - Venkova, K
AU  - Venkova K
FAU - Keith, J C Jr
AU  - Keith JC Jr
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Interleukin-11)
RN  - 0 (Recombinant Proteins)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Animals
MH  - Colon/pathology/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Enteritis/*pathology/*physiopathology
MH  - Feces
MH  - HLA-B27 Antigen/*genetics
MH  - Interleukin-11/*pharmacology
MH  - Jejunum/pathology/*physiology
MH  - Muscle Contraction/drug effects/physiology
MH  - Muscle, Smooth/*drug effects
MH  - Parasympathetic Nervous System/drug effects/physiology
MH  - Peroxidase/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Recombinant Proteins/pharmacology
EDAT- 2001/09/19 10:00
MHDA- 2001/10/19 10:01
CRDT- 2001/09/19 10:00
PHST- 2001/09/19 10:00 [pubmed]
PHST- 2001/10/19 10:01 [medline]
PHST- 2001/09/19 10:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2001 Oct;299(1):58-66.