Treatment of concanavalin A-induced hepatitis in mice with low molecular weight heparin.
OBJECTIVE
Heparin has been noted to inhibit inflammation independent of its known anti-coagulant activity. In the present study, we examined the ability of heparin and low molecular weight heparin to prevent immune-mediated, concanavalin A-induced liver damage.


METHODS
Mice were pretreated with either heparin or low molecular weight heparin (Fragmin) prior to their inoculation with concanavalin A (10 mg/kg). Liver enzymes, liver histology, and the serum levels of tumor necrosis factor-a, interleukin-6, and interleukin-10 were examined in the control and treated mice.


RESULTS
The histopathologic damage in the liver, and the concanavalin A-induced release of aminotransferases, tumor necrosis factor-a, and interleukin-6 were significantly inhibited in mice pretreated with low molecular weight heparin, whereas the serum levels of the anti-inflammatory cytokine interleukin-10 were increased (p<0.01). Interestingly, maximal inhibition was obtained with low low molecular weight heparin doses (5 and 1 microg/mouse, p<0.001), while higher doses were less effective. Concanavalin A-induced liver injury was not prevented by pretreatment of the mice with heparan sulphate (p<0.001), which although it is structurally similar to heparin possesses neither anti-inflammatory nor anti-coagulant properties.


CONCLUSIONS
This study demonstrates the efficacy of low molecular weight heparin in preventing immune-mediated liver damage in mice.
Hershkoviz
R
R
Department of Gastroenterology, The Tel-Aviv Sourasky Medical Center, Israel.
Bruck
R
R
Aeed
H
H
Shirin
H
H
Halpern
Z
Z
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003208:Concanavalin A; D006493:Heparin / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006520:Hepatitis, Animal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006495:Heparin, Low-Molecular-Weight; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D016753:Interleukin-10; D006493:Heparin; D000410:Alanine Transaminase