Interferon-gamma treatment accelerates and aggravates autoimmune pancreatitis in the MRL/Mp-mouse

Background: T helper 1 cell-released pro-inflammatory cytokines have been implicated in the pathogenesis of autoimmune pancreatitis (AIP), but the experimental database is small. Here, we have directly tested the effects of interferon-γ (IFN-γ) by applying it to AIP-prone MRL/Mp mice. Methods: MRL/Mp-mice were treated for 4 weeks with IFN-γ. Severity of AIP was assessed by histopathology, laboratory findings and gene expression analysis. Results: Using a histopathological score from 0 (healthy pancreas) to 4 (severe AIP), we found that IFN-γ treatment strongly increased severity of pancreatic lesions. IFN-γ also caused pancreatic accumulation of CD4-, CD8-, C11b- and CD138-positive cells, and enhanced pancreatic mRNA expression of interleukin (IL)-1β, transforming growth factor-β and IFN-γ itself. In the serum of IFN-γ-treated mice, higher lipase activities but normal glucose levels were observed. Discussion: IFN-γ accelerates and aggravates AIP in MRL/Mp mice. IFN-γ-enhanced AIP of MRL/Mp mice may serve to study pathophysiology, and to test diagnostic/therapeutic approaches.