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-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.


CONCLUSIONS
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.
Fitzner
Brit
B
Department of Medicine, Division of Gastroenterology, University of Rostock, Rostock, Germany.
Holzhueter
Stephanie-Anna
SA
Ibrahim
Saleh
S
Nizze
Horst
H
Jaster
Robert
R
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000009:adverse effects*; D008049:Lipase / Q000235:genetics; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D010195:Pancreatitis / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D000516:alpha-Amylases / Q000235:genetics
D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D007371:Interferon-gamma; D008049:Lipase; D000516:alpha-Amylases