Treatment of concanavalin A-induced hepatitis in mice with low molecular weight heparin

Background/Aims: Heparin has been noted to inhibit inflammation independent of its known anti-coagulant activity. In the present study, we examined th e ability of heparin and low molecular weight heparin to prevent immune-med iated, concanavalin A-induced liver damage. Methods: Mice were pretreated with either heparin or low molecular weight h eparin (Fragmin) prior to their inoculation with concanavalin A (10 mg/kg). Liver enzymes, liver histology, and the serum levels of tumor necrosis fac tor-alpha, interleukin-6, and interleukin-10 were examined in the control a nd treated mice. Results: The histopathologic damage in the liver, and the concanavalin A-in duced release of aminotransferases, tumor necrosis factor-alpha, and interl eukin-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 w as obtained with low low molecular weight heparin doses (5 and 1 mu g/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 sul phate (p<0.001), which although it is structurally similar to heparin posse sses neither anti-inflammatory nor anti-coagulant properties. Conclusions: This study demonstrates the efficacy of low molecular weight h eparin in preventing immune-mediated liver damage in mice.