PMID- 14569059
OWN - NLM
STAT- MEDLINE
DCOM- 20040211
LR  - 20171116
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 308
IP  - 1
DP  - 2004 Jan
TI  - Oral treatment with recombinant human interleukin-11 improves mucosal transport 
      in the colon of human leukocyte antigen-B27 transgenic rats.
PG  - 206-13
AB  - Recombinant human interleukin (IL)-11 is a pleiotropic cytokine with 
      anti-inflammatory activity. The objective of the study was to investigate whether 
      oral treatment with rhIL-11 improves colonic epithelial dysfunction in the human 
      leukocyte antigen (HLA)-B27 transgenic rat model of spontaneous chronic 
      inflammation. Experiments were performed using adult male HLAB27 rats, whereas 
      healthy nontransgenic F344 rats served as controls. Enteric-coated rhIL-11 
      multi-particles (equivalent to 500 microg/kg rhIL11) or placebo (formulation 
      lacking rhIL-11) were administrated orally on alternate days for 2 weeks to 
      HLA-B27 or F344 rats. Stool character was observed daily during the treatment 
      period. Animals were euthanized at the end of treatment and colonic inflammation 
      was evaluated be measuring tissue myeloperoxidase (MPO) activity. Epithelial 
      transport in isolated colonic mucosal sheets was studied in modified Ussing 
      chambers. Oral treatment of HLA-B27 rats with rhIL-11 reduced MPO activity in the 
      colon and suppressed the clinical signs of diarrhea. The electrophysiological 
      characteristics of mucosal transport were improved in the HLA-B27 rats treated 
      with rhIL-11 compared with placebo. After rhIL-11 treatment the basal 
      transepithelial resistance and the estimated paracellular resistance were 
      significantly increased, neurally mediated secretory responses to electrical 
      field stimulation were improved, and cholinoceptor sensitivity was normalized. 
      Treatment with rhIL-11 had no significant effect on basal short circuit current 
      and the maximal secretory response to carbachol or substance P. Our data 
      demonstrate that oral rhIL-11 therapy is associated with suppression of mucosal 
      inflammation and a concomitant improvement of epithelial resistance and neurally 
      mediated secretion in a model of chronic HLA-B27 colitis.
FAU - Venkova, Kalina
AU  - Venkova K
AD  - Oklahoma Foundation for Digestive Research Basic Science Laboratories, Veterans 
      Affairs Medical Center, Oklahoma City, Oklahoma 73104, USA.
FAU - Keith, James C Jr
AU  - Keith JC Jr
FAU - Greenwood-Van Meerveld, Beverley
AU  - Greenwood-Van Meerveld B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031020
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  - 33507-63-0 (Substance P)
RN  - 8Y164V895Y (Carbachol)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - HM5641GA6F (oprelvekin)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - Carbachol/pharmacology
MH  - Colon/*drug effects/enzymology/metabolism
MH  - Drug Interactions
MH  - HLA-B27 Antigen/genetics/*immunology
MH  - Humans
MH  - Interleukin-11/*pharmacology
MH  - Intestinal Mucosa
MH  - Male
MH  - Mucous Membrane
MH  - Peroxidase/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Recombinant Proteins/*pharmacology
MH  - Substance P/pharmacology
EDAT- 2003/10/22 05:00
MHDA- 2004/02/12 05:00
CRDT- 2003/10/22 05:00
PHST- 2003/10/22 05:00 [pubmed]
PHST- 2004/02/12 05:00 [medline]
PHST- 2003/10/22 05:00 [entrez]
AID - jpet.103.058701 [pii]
AID - 10.1124/jpet.103.058701 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2004 Jan;308(1):206-13. doi: 10.1124/jpet.103.058701. Epub 
      2003 Oct 20.