5.3 Tumor necrosis factor alpha

In response to an infectious stimuli, such as lipopolysaccharides (LPS), tumor necrosis factor α (TNF-α) is a cytokine that is released early mainly by macrophages, and it is a principal mediator of the inflammatory response to infection which stimulates acute inflammation by its action on different cells, such as endothelial cells and leukocytes [50].

Many studies have been done in an attempt to determine if specific SNPs in the TNF alpha factor gene are implicated in sepsis susceptibility with conflicting results. A recent meta-analysis from Zhang et al. [51] which included 23 articles that evaluated the effects of TNF-α rs1800629 and rs361525 polymorphisms on sepsis risk found that TNF-α rs1800629 was associated with increased sepsis risk in the overall population in four genetic models, including adenosine (A) vs. guanine (G) (p < 0.001, odds ratio (OR) = 1.32), GA vs. GG (p < 0.001, OR = 1.46), GA + AA vs. GG (p < 0.001, OR = 1.46), and carrier A vs. carrier G (p < 0.001, OR = 1.32). These results suggest an implication of these genetic variations with an increased susceptibility for sepsis development.
