Vitamin D3-Mediated Cytokine Modulation Is Beneficial in Severe Acute Experimental Pancreatitis
Abstracts
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Background: The release of various cytokines contributes to systemic morbidity during the early stage of severe acute pancreatitis. In the transplant setting, Vitamin D3 (VD3; 1alpha,25dihydroxy cholecalciferol) has been found to modify the cytokine response (Hepatology 2001;34:926). The aim of this study was to test the effects of VD3 on the cytokine response in a model of necrotizing acute pancreatitis (NP) in rats. Methods: In female Wistar rats NP was induced by pressure and volume controlled infusion of 5% sodium-taurocholate into the biliopancreatic duct . Rats were allocated to 3 groups: Control (n=6), NP followed by placebo i.p.(n=8) and NP followed by VD3 i.p. 20 min after induction of NP (n=8). In a parallel experiment three day mortality was determined in 29 animals with NP and VD3 or placebo. Serum, pancreas, lung and liver tissue were analyzed using commercially available assays for interleukin (IL)-1ß (pro-inflammatory), IL-10 (anti-inflammatory) and IL-12 (immunomodulating) three hours after induction of NP. Lung and pancreatic tissue was assessed for myeloperoxidase (MPO) and histology. Results: Histology and MPO assay confirmed significant acute pancreatitis and neutrophil infiltration in NP animals. Cytokines in serum, pancreas, lung and liver markedly increased in animals with NP as compared to control rats. VD3 lowered the peak levels of IL-1 and IL-12 and modified the cytokine response by decreasing the pro-/anti-inflammatory ratio. This effect was more prominent in pancreas and lung tissue than in liver tissue and serum. 72-h mortality was 25% in VD3-treated NP rats versus 86% in NP rats receiving placebo (p<0.01; Fischers exact test). Conclusions: VD3 interferes with the cytokine response seen in severe acute pancreatitis and lowers mortality. The beneficial effects may be due to decreased leukocyte infiltration and a relative increase of IL-10 levels. |
