Dexamethasone enhances mallory body formation in drug-primed mouse liver

In a clinical study in which patients with alcoholic hepatitis were treated with prednisone for 1 month, posttreatment liver biopsies showed diminished inflammation, but Mallory bodies were not diminished. This suggested that steroid treatment may reduce inflammation by inhibiting NFκB activation. Sparing of Mallory bodies suggests that NFκB activation may not be involved mechanistically in Mallory body formation. To test this idea, we induced Mallory body formation in drag-primed mice with or without dexamethasone treatment. As predicted, dexamethasone decreased NFκB activation; however, Mallory body formation was increased. Surprisingly, TNFα and iNOS, which normally increase as a result of NFκB activation, were upregulated by the dexamethasone treatment. It was concluded that NFκB activation is not involved in Mallory body formation. Despite this, induced increases in TNFα, iNOS, c-jun/API and c-myc expression indicate that oxidative stress is likely involved in Mallory body formation. (C) 2000 Academic Press.