The TNF-α (–238 G/A) polymorphism could protect against development of severe sepsis

Abstract

Primary responses in sepsis-mediated inflammation are regulated by pro-inflammatory cytokines. Variations in the cytokine genes might modify their transcription or expression, plasma cytokines levels and response to sepsis. Activation protein-1 (AP-1) and NF-κB regulate cytokines gene expression in sepsis. A total of 90 severely septic and 91 non-infected patients were prospectively studied. IL-1α ( –889 C/T), IL-1β ( +3954 C/T), IL-6 ( –174 G/C), TNF-α ( –238 G/A), TNF-α ( –308G/A), IL-8 ( –251A/T) and IL-10 ( –1082 G/A) SNPs, plasma IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-γ, TNF-α and monocyte chemoattractant protein 1 (MCP-1) levels, and AP-1 and NF-κB gene expression by neutrophils were assessed. A allele carriers of TNF-α ( –238 G/A) SNP were less frequent among septic patients. IL-6, IL-8, IL-10, TNF-α and MCP-1 levels were higher, and AP-1 and NF-κB gene expressions lower in septic patients. Sepsis was independently associated with higher fibrinogen, neutrophils counts and IL-8 levels, lower prothrombin, absence of the variant A allele of the TNF-α (–238 G/A) SNP, and haemodynamic failure. Death was independently associated with a higher APACHE II score, higher IL-8 levels, and the diagnosis of sepsis. TNF-a ( –238 G/A) SNP could protect against sepsis development. Higher IL-8 levels are predictive of sepsis and mortality.

Anti‐fibrinolytic agent tranexamic acid suppresses the endotoxin‐induced expression of Tnfα and Il1α genes in a plasmin‐independent manner

“…17,18 Moreover, TNFα gene polymorphism could protect against the development of severe sepsis in humans. 19 On the other hand, IL1α, but not IL1β was shown to drive IL1R1-dependent sepsis lethality in neonatal mice. 20 Based on these data, further animal studies assessing the efficiency of TXA protection against sepsis should be considered.…”

“…The LPS stimulation of TNF α expression in the liver is known to induce hepatocyte apoptosis, liver failure, and even lethal effect 17,18 . Moreover, TNF α gene polymorphism could protect against the development of severe sepsis in humans 19 . On the other hand, IL1 α , but not IL1 β was shown to drive IL1R1‐dependent sepsis lethality in neonatal mice 20 .…”

Simplified Immune-Dysregulation Index: A Novel Marker Predicts 28-Day Mortality of Intensive Care Patients With Sepsis

“…IL-6/LY# ratio act like a microcosm of the immune system. There are still many inflammatory factor and cytokines may provide us with more information during the occurrence and development of sepsis, such as IL-8, IL-10, and TNF-α (29)(30)(31). Studies contains varies cytokines and inflammatory biomarkers should be carried out to explore interactions between the hyperinflammatory state and subtypes of T-cell transition in patients with sepsis.…”

Glycyrrhizic Acid Protects Experimental Sepsis Rats against Acute Lung Injury and Inflammation

“…This paper observed that GA reduced the degrees of TNF- α , IL- β , and HMGB1 by ELISA. The levels of TNF- α and MCP-1 in plasma of 90 patients with severe sepsis were higher than those in the controls [ 28 ]. It was pointed out that improving inflammation can treat lung function and tissue injury.…”