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Relevance of transforming growth factor-β1, interleukin-8, and tumor necrosis factor-α polymorphisms in patients with chronic pancreatitis Volume 18, numéro 1, March 2007

Auteurs
Department of Surgery, University of Szeged, Hungary, Department of Medical Microbiology and Immunobiology, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary, Department of Internal Medicine, University of Szeged, Hungary

Cytokine regulation may be an important factor in the susceptibility for the development of chronic pancreatitis; transforming growth factor-β1 (TGF-β1) plays a central role in the pathogenesis of pancreatic fibrogenesis. The aim of our study was to analyse the relevance of TGF-β1, interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) polymorphisms in patients with chronic pancreatitis.Patients: of the 83 patients enrolled in the study, 43 were treated medically and 40 patients underwent surgical intervention. Healthy blood donors (n = 75) served as controls.Methods: the polymorphisms of TGF-β1 +869 T→ C and IL-8 -251 T→A were determined by the ARMS method, while that of TNF-α -308 was investigated using NcoI RFLP.Results: there was a higher frequency (50%) of the TT genotype of TGF-β1 +869, with a concomitantly higher TGF-β1 level in the plasma (5.2 ± 1.7 ng/mL) of patients with chronic pancreatitis than in healthy blood donors (28% and 2.8 ± 0.9 ng/mL respectively). The number of TT homozygotes differed significantly between the patients who underwent surgical intervention and the controls, and even between the surgical and the non-surgical patients. The frequency of the T/A genotype with higher IL-8 production, was significantly higher in both groups of patients than in the controls (58% and 58% versus 40%). No correlation was found between the TNF-α -308 polymorphism and chronic pancreatitis.Conclusions: correlations of the TGF-β1 and IL-8 single nucleotide polymorphisms (SNPs) with chronic pancreatitis underline the importance of these cytokines in the pathomechanism of the disease. Moreover, it seems that the TT genotype of +869 TGF-β1 might be a risk factor for the development of a severe form of chronic pancreatitis, and could serve as a prognostic sign for any future surgical intervention or even repeat surgery. Further studies on a larger group of patients, in addition to a follow-up study, are necessary to confirm this preliminary observation.