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 (TNFα) 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, TaiI restriction enzymes.

Results: Mean plasma TNFα level in healthy Control group was 8.37 ± 2.23 pg/ml, in SIRS group, the mean plasma TNFα 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.