Polymorphism in the IL-8 gene, but not in the TLR4 gene, increases the severity of acute pancreatitis

Background/Aim: Activated granulocytes and inflammatory mediators of the innate immune response play fundamental roles in the pathogenesis of acute pancreatitis. We studied whether polymorphisms of interleukin-8 (IL-8) and Toll-like receptor 4 (TLR4) genes correlate with the severity of acute pancreatitis. Methods: Patients with acute pancreatitis (n = 92) were grouped according to the severity of the disease on the basis of the Ranson scores. Healthy blood donors ( n = 200) served as controls. The IL-8 - 251 gene polymorphism was analyzed by amplification-refractory mutation system; the single-nucleotide polymorphisms (Asp299Gly and Thr399Ile) of TLR4 were investigated by using a real-time polymerase chain reaction method with melting point analysis. Results: The IL-8 A/T heterozygote mutant variants were detected with a significantly higher frequency among the patients with severe pancreatitis than among the healthy blood donors ( 60 vs. 42%; p = 0.0264, odds ratio = 2.071, 95% confidence interval = 1.101 - 3.896), while the frequency of the normal allelic genotype ( TT) was higher among the patients with mild pancreatitis than in the group with severe pancreatitis ( 35 vs. 16%; p = 0.051, odds ratio = 2.917, 95% confidence interval = 1.089 - 7.811). There was no significant correlation between TLR4 polymorphisms and the acute pancreatitis itself, but nonsignificantly increased frequencies of Asp299Gly and Thr399Ile heterozygotes among patients with severe infected pancreatic necrosis could be observed relative to the patients with mild pancreatitis. Conclusions: Determination of the frequency of IL-8 polymorphism in acute pancreatitis may be informative and may provide further evidence concerning the role of IL-8 in the severe form of this disease. The possible role of TLR4 polymorphism in the outcome of severe acute pancreatitis requires further investigations in a larger series of patients. Copyright (C) 2006 S. Karger AG, Basel and IAP.