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-gamma (IFN-gamma) by applying it to AIP-prone MRL/Mp mice. METHODS: MRL/Mp-mice were treated for 4 weeks with IFN-gamma. 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-gamma treatment strongly increased severity of pancreatic lesions. IFN-gamma also caused pancreatic accumulation of CD4-, CD8-, C11b- and CD138-positive cells, and enhanced pancreatic mRNA expression of interleukin (IL)-1 beta, transforming growth factor-beta and IFN-gamma itself. In the serum of IFN-gamma-treated mice, higher lipase activities but normal glucose levels were observed. DISCUSSION: IFN-gamma accelerates and aggravates AIP in MRL/Mp mice. IFN-gamma-enhanced AIP of MRL/Mp mice may serve to study pathophysiology, and to test diagnostic/therapeutic approaches. (c) 2009 S. Karger AG, Basel.
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-gamma (IFN-gamma) by applying it to AIP-prone MRL/Mp mice. METHODS: MRL/Mp-mice were treated for 4 weeks with IFN-gamma. 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-gamma treatment strongly increased severity of pancreatic lesions. IFN-gamma also caused pancreatic accumulation of CD4-, CD8-, C11b- and CD138-positive cells, and enhanced pancreatic mRNA expression of interleukin (IL)-1 beta, transforming growth factor-beta and IFN-gamma itself. In the serum of IFN-gamma-treated mice, higher lipase activities but normal glucose levels were observed. DISCUSSION: IFN-gamma accelerates and aggravates AIP in MRL/Mp mice. IFN-gamma-enhanced AIP of MRL/Mp mice may serve to study pathophysiology, and to test diagnostic/therapeutic approaches. (c) 2009 S. Karger AG, Basel.