Protective effect of low molecular weight heparin on experimental colitis: role of neutrophil recruitment and TNF-alpha production.
OBJECTIVE
The purpose of this study was to examine the impact and mechanism of action of low molecular weight heparin (LMWH) in a model of murine colitis.


METHODS
Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for five days. LMWH (500 units/kg/day) was administered by subcutaneous injection prior to and throughout the treatment period with DSS. Clinical disease activity index (DAI), including body weight loss, stool consistency and blood in feces were examined daily. Moreover, crypt height (CH), mucosal damage score (MDS), myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-alpha) content in the colon were determined.


RESULTS
DSS increased DAI, MDS, MPO activity and TNF-alpha production and decreased CH. Administration of LMWH markedly reduced DAI, MDS and reversed the CH-reduction. Moreover, in LMWH-treated animals, the MPO activity was reduced by more than 67% whereas mucosal levels of TNF-alpha was similar compared to DSS control mice.


CONCLUSIONS
These findings suggest that LMWH inhibits murine colitis by interference with neutrophil recruitment and that LMWH may provide a novel pharmacological approach to treatment of inflammatory bowel disease.
Wan
M X
MX
Department of Surgery, Malmö University Hospital, Lund University, Sweden.
Liu
Q
Q
Wang
Y
Y
Thorlacius
H
H
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate; D004797:Enzyme-Linked Immunosorbent Assay; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D009195:Peroxidase