Endogenous αCGRP protects against concanavalin A-induced hepatitis in mice

To evaluate hepatoprotective effect of α-calcitonin gene-related peptide (αCGRP), we compared the susceptibilities of αCGRP−/− and wild-type mice to concanavalin A (Con A)-induced hepatitis. Twelve hours after Con A administration, serum transaminases were markedly higher in αCGRP−/− than wild-type mice, and much more extensive TUNEL-positive lesions and DNA fragmentation were detected in the livers of αCGRP−/− mice. Notably, expression of IL-6 was selectively diminished in αCGRP−/− mice, suggesting that induction of IL-6 during acute inflammatory responses is blunted in αCGRP−/− mice. In addition, primary cultured αCGRP−/− hepatocytes were more susceptible to IFN-γ-induced cell death than hepatocytes from wild-type mice. Administration of exogenous αCGRP reduced the incidence of apoptosis among hepatocytes and endothelial cells. It thus appears that αCGRP exerts a hepatoprotective effect by modulating cytokine expression and preventing apoptosis.