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The toxicity caused by different organisms in septic shock is substantially complex and characterized by an intricate pathogenicity that involves several systems and pathways. Immune cells’ pattern recognition receptors initiate the host response to pathogens after the recognition of pathogen-associated molecular patterns. In essence, the subsequent activation of downstream pathways may progress to infection resolution or to a dysregulated host response that represents the hallmark of organ injury in septic shock. Likewise, the management of organism toxicity in septic shock is complicated and comprises a multiplicity of suitable targets. In this review, the classic immune responses to pathogens are discussed as well as other factors that are relevant in the pathogenicity of septic shock, including sepsis-induced immune suppression, inflammasome activation, intestinal permeability, and the role of lipids and proprotein convertase subtilisin/kexin type 9. Current therapies aiming to eliminate the organisms causing septic shock, recent and ongoing trials in septic shock treatment, and potential new therapeutic strategies are also explored.

Background: The IL10 family of genes includes crucial immune regulators. We tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19, IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of septic shock. Methods: Patients with septic shock (n = 1,193) were genotyped for 13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in genotyped lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n = 981) were genotyped for IL20 rs2981573 A/G. The primary outcome variable was 28-day mortality. Results: Patients with the G allele of IL20 rs2981573 had a significantly increased hazard of death over the 28-day period compared to patients with the A allele in the septic shock cohort (adjusted hazard ratio 1.27; 95% confidence interval 1.10-1.47; p = 8.0 × 10-4). Patients with the GG genotype had more organ dysfunction (p < 0.05). The GG genotype was associated with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro (p < 0.05). The cardiac surgical ICU patients with the GG genotype had an increased length of ICU stay (p = 0.032). Conclusions: The GG genotype of IL20 rs2981573 SNP was associated with increased IL20 gene expression and increased adverse outcomes in patients with septic shock and following cardiac surgery.

The IL10 family of genes includes crucial immune regulators. We tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19, IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of septic shock.Patients with septic shock (n = 1,193) were genotyped for 13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in genotyped lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n = 981) were genotyped for IL20 rs2981573 A/G. The primary outcome variable was 28-day mortality.Patients with the G allele of IL20 rs2981573 had a significantly increased hazard of death over the 28-day period compared to patients with the A allele in the septic shock cohort (adjusted hazard ratio 1.27; 95% confidence interval 1.10-1.47; p = 8.0 × 10-4). Patients with the GG genotype had more organ dysfunction (p0.05). The GG genotype was associated with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro (p0.05). The cardiac surgical ICU patients with the GG genotype had an increased length of ICU stay (p = 0.032).The GG genotype of IL20 rs2981573 SNP was associated with increased IL20 gene expression and increased adverse outcomes in patients with septic shock and following cardiac surgery.