METHYLPREDNISOLONE DOES NOT INHIBIT THE NONPARENCHYMAL CELL RESPONSESTO DIMETHYLNITROSAMINE-INDUCED LIVER-INJURY

Corticosteroids are used as anti-inflammatory agents in many chronic d isorders including liver disease. We have investigated the effects of methylprednisolone treatment on the monocyte/macrophage and hepatic st ellate cell responses to liver injury produced in rats by administrati on of dimethylnitrosamine (DMN), Animals were treated in the following groups (six per group): no treatment (controls), methylprednisolone a lone (20 mg/kg i.p. on 3 days), DMN alone (six doses of 8 mg/kg by int ragastric lavage), and methylprednisolone/DMN. Non-parenchymal cells w ere identified immunohistochemically; cells were counted per unit area (0.635 mm(2)). Following DMN treatment there was a dramatic increase compared to control livers in the numbers of ED1- and ED2-positive mon ocytes/macrophages, and desmin-and or-smooth muscle actin(alpha-SMA)-p ositive hepatic stellate cells in the damaged perivenular zones. Methy lprednisolone treatment in DMN-treated rats was not associated with an y change in the number of ED1- or ED2-positive monocytes/macrophages o r desmin-positive hepatic stellate cells compared to animals given DMN alone, There was, however, a rise in the number of alpha-SMA-positive hepatic stellate cells in methylprednisolone/DMN treated animals comp ared to those given DMN alone. In conclusion, this study has shown no anti-inflammatory effect of methylprednisolone treatment during DMN-in duced acute experimental liver injury. The increase in alpha-SMA-posit ive hepatic stellate cells following methylprednisolone suggests that corticosteroids may be associated with enhanced hepatic stellate cell proliferation and/or 'activation'.