The Relationship Between Nuclear Factor-КB And Acute Pancreatitis In Patients

Background: Many experimental studies have shown that NF-кB activation is a pivotal step in the pathogenesis of acute pancreatitis(AP), and cytokines are involved in the process of the disease, NF-кB may be a potential target for modulation in the therapy of AP, but related clinical researches have been few reported. Objectives: To investigate the expression of NF-кB in peripheral blood polymorphonuclear leukocyte (PMN) and the interaction between activated NF-кB and serum cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), IL-8 and IL-10 of patient with AP. And to assess the preventive effectiveness of pyrrolidine dithiocarbamate (PDTC) on NF-кB in vitro.Methods: Nineteen patients were enrolled in this study and were divided into MAP(n=10)and SAP(n=9)groups according to Ranson criteria, and 16 healthy individuals were also included as control subjects. Peripheral venous blood samples were collected into EDTA tubes and no-EDTA tubes respectively at admission and days 3 during hospitalization (control groups only once), total 10ml every time, and were immediately processed for isolation of serum, plasma(AP patients only) and PMNs. PMNs were used rapidly for the preparation of nuclear extracts with pretreatment of various concentrations of PDTC. In vitro inhibition experiments using NF-кB inhibitor PDTC were also performed. The expression of NF-кB in PMNs was determined by gel electrophoretic mobility shift assay(EMSA), and the serum levels of IL-6, 8, 10 and TNF-α were detected by enzyme linked immunosorbent assay(ELISA). Routine clinical assessments (full blood count, gas analysis, biochemical examination, serum amylase and findings of pancreatitis on computed tomography) were recorded for all patients. Results: At admission, the full blood PMN count of patients with AP increased significantly (P<0.01 vs. control group), group SAP increased more higher(P<0.05 vs. group MAP), and the PMNs from the patients with AP showed higher levels of NF-кB activities than did those from control subjects(P<0.01), group SAP showed much higher than MAP group(P<0.05), and the levels of NF-кB activities in the control ones were much lower. Meanwhile, the serum levels of IL-6, 8, 10 and TNF-α of AP patients elevated remarkably comparing with control group(P<0.01). IL-6, 8 and TNF-α were positively correlated with NF-кB activity(r= 0.787, 0.837, 0.825; P<0.01), while IL-10 not(r=0.468, P>.05). Simultaneously, IL-6, 8 and TNF-α had correlations mutually(IL-6 vs. IL-8,r= 0.924; IL-6 vs. TNF-α,r= 0.636; IL-8 vs. TNF-α,r= 0.718; P<0.01). At day 3, the expression levels of NF-кB activity and above cytokines all decreased, but were still very high with patients who subsequently developed serious systemic complications. In vitro, PDTC could reduce the NF-кB activity of PMNs from patients with AP, and the effectiveness differences between 2mM and 1mM were observed(P<0.05), the former seemed stronger. Also, the PMNs from control subjects pretreated with 2mM PDTC before stimulation with the plasma from patients with SAP showed lower levels of NF-кB activities than did those unpretreated (P<0.05).Conclusions: The NF-кB activation in peripheral blood PMNs participate in the clinical course of acute pancreatitis with the ability controlling cytokines transcription and may be a marker predisposing the severity of AP. Therapy aimed at attenuating NF-кB activation may contribute to the prognosis of AP.