Association between Genetic Polymorphisms of Inflammatory Response Genes and Acute Pancreatitis.

Inflammation plays a central role in the pathophysiology of acute pancreatitis (AP). We hypothesized that changes in the function of key components of the inflammatory cascade, caused by genetic polymorphisms, could determine the development and/or severity of AP. We studied the following polymorphisms in 269 patients: IL23R rs11209026, TNF rs1800629, RIPK2 rs42490, NOD2 rs9302752, MCP1 rs1024611 and NFKB1 rs28362491. The rs11209026 A allele was related to the presence of AP (p = 0.007261; OR = 1 .523). Epistasis analysis revealed that AP susceptibility was increased by interaction between IL23R rs11209026 and TNF rs1800629 (p = 1.205 × 10-5; ORinteraction = 4.031). The rs42490-G allele was associated with an increased risk of severe pancreatitis (p = 0.01583; OR = 2.736), severe or moderately severe pancreatitis (p = 0.04206; OR = 1.609), and death (p = 0.03226; OR = 3.010). In conclusion, these results point to a plausible role for genetic polymorphisms in IL23R and RIPK2 in the development and severity of AP.

TH1 and TH2 Cytokine Profiles as Predictors of Severity in Acute Pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) is severe in up to 20% of patients, with a high mortality rate. Quantification of serum TH1 and TH2 cytokines may provide objective evidence to assess the severity of AP and predict its course. METHODS: One hundred seventeen patients were studied, measuring serum concentrations of interleukin (IL)1ß, IL2, IL4, IL5, IL6, IL10, IL12p70, IL13, IL18, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN) γ, and tumor necrosis factor (TNF) α. RESULTS: Significant differences were found between patients with severe AP and those with mild or moderately severe AP in IFN-γ (P < 0.001), IL6 (P < 0.001), TNF-α (P = 0.002), GM-CSF (P < 0.001), IL4 (P = 0.002), IL1b (P = 0.017), and IL13 (P < 0.001) concentrations. Interferon-γ, IL6, and TNF-α were associated with severe AP, whereas GM-CSF, IL4, IL1b, and IL13 were associated with mild or moderately severe AP. The IL13/IFNγ ratio was significantly higher in patients with mild AP (P = 7.36 × 10). CONCLUSIONS: A TH1 profile was associated with severe AP and a TH2 profile with mild or moderately severe AP. We report an IL13/IFNγ ratio of potential value to predict the prognosis in AP.

BISAP, RANSON, lactate and others biomarkers in prediction of severe acute pancreatitis in a European cohort.

BACKGROUND AND AIM: The study aims to assess and compare the predicting ability of some scores and biomarkers in acute pancreatitis. METHODS: We prospectively collected data from 269 patients diagnosed of acute pancreatitis, admitted to Virgen de las Nieves University Hospital between June 2010 and June 2012. Blood urea nitrogen (BUN), C-reactive protein, and creatinine were measured on admission and after 48 h, lactate and bedside index for severity acute pancreatitis (BISAP) only on admission and RANSON within the first 48 h. Definitions from 2012 Atlanta Classification were used. Area under the curve (AUC) was calculated for each scoring system for predicting severe acute pancreatitis (SAP), mortality, and intensive care unit (ICU) admission, obtaining optimal cut-off values from the receiver operating characteristic curves. RESULTS: Eight (3%) patients died, 17 (6.3%) were classified as SAP, and 10 (3.7%) were admitted in ICU. BISAP was the best predictor on admission for SAP, mortality, and ICU admission with an AUC of 0.9 (95% CI 0.83-0.97); 0.97 (95% CI 0.95-0.99); and 0.89 (95% CI 0.79-0.99), respectively. After 48 h, BUN 48 h was the best predictor of SAP (AUC = 0.96 CI: 0.92-0.99); BUN 48 h and BISAP were the best predictors for mortality (AUC = 0.97 CI: 0.95-0.99) and creatinine 48 h for ICU admission (AUC = 0.96 CI: 0.92-0.99). Lactate showed an AUC of 0.79 (CI: 0.71-0.88), 0.87 (CI: 0.78-0.96), and 0.77 (CI: 0.67-0.87) for SAP, mortality, and ICU admission, respectively. All parameters were predictors for SAP, mortality, and ICU admission, but C-reactive protein on admission was only a significant predictor of SAP. CONCLUSION: Bedside index for severity acute pancreatitis is a good predictive system for SAP, mortality, and ICU admission, being useful for triaging patients for ICU management. Lactate could be useful for developing new scores.

The role of Toll-like receptor polymorphisms in acute pancreatitis occurrence and severity.

OBJECTIVES: Toll-like receptors (TLRs) are damage-associated molecular patterns receptors, which are essential in the activation of the inflammasome cascade, required for the initiation of inflammation. We hypothesized that changes in the function of these receptors caused by genetic polymorphisms in their encoding genes could determine acute pancreatitis (AP) incidence or severity. METHODS: Two hundred sixty-nine patients and 269 controls were included. Acute pancreatitis diagnosis criteria were abdominal pain, increased serum amylase levels, and positive findings on abdominal imaging. The patients were observed until discharge. Blood samples were obtained, determining the following TLRs: TLR1 rs5743611, TLR2 rs5743704, TLR3 rs3775291, TLR3 rs5743305, TLR4 rs4986790, TLR4 rs4986791, TLR5 rs5744174, TLR6 rs5743795, TLR7 rs2302267, TLR9 rs352140, and TLR10 rs4129009. RESULTS: No TLR polymorphism was related to AP incidence. Regarding severity, CC genotype patients in TLR3 rs3775291 had an increased risk for severe pancreatitis (CC odds ratio [OR], 2.426; P = 0.015). In addition, TLR6 rs5743795 GG genotype patients had a lower risk for severe AP (GG OR, 0.909; P < 0.05). Intensive care unit admission was related to TLR5 rs5744174 homozygote TT carriers (TT OR, 3.367; P = 0.036). CONCLUSIONS: Our article points to genetic polymorphisms in TLR3 and TLR6 as having a plausible role in the occurrence of severe AP.