Tumor Necrosis Factor gene polymorphism results in high TNF level in sepsis and septic shock

Introduction: Systemic sepsis releases several cytokines among which tumor necrosis factor alfa (TNF alpha) has emerged as key cytokine causing septic shock. Single Nucleotide Polymorphisms (SNPs) at positions -238, -308, -376 and +489 in the promoter region of TNF gene exhibit differential association to inflammation and increased TNF production in sepsis. Materials and Methods: This research work was carried out in 278 critically ill patients and 115 controls. The patients were divided into four groups: Healthy controls, SIRS, Sepsis and Septic shock. Plasma cytokine level was evaluated by ELISA. Specific sequences of TNF gene (-238, -308, -376, +489) were amplified using polychromase chain reaction (PCR). SNP detected by BamHiI, NcoI, FokI, Tail restriction enzymes. Results: Mean plasma TNF alpha level in healthy Control group was 8.37 +/- 2.23 pg/ml, in SIRS group, the mean plasma TNF alpha level was 77.99 +/- 5.51 pg/ml, in Sepsis patients 187.1 +/- 14.33 pg/ml and in septic shock 202.2 +/- 14.85 pg/ml; range 56.17-417.1 pg/ml. SNP was studied among different patient groups, which showed a higher frequency of mutants among sepsis and shock patients as compared to control. Conclusion: Plasma TNF alpha level was significantly high in patients with sepsis and septic shock. SNP of TNF gene showed significant association between polymorphism and development of severe sepsis and septic shock, this would help us in evaluating patients at high risk for septic shock and such patients needed to obtain a rational basis for therapy. Crown Copyright (c) 2012 Published by Elsevier Ltd. All rights reserved.