TNF-α<sub>-238</sub> (rs 361525) SNP was performed by RT-PCR on 200 critically-ill patients (112 had severe sepsis and septic shock and 88 were septic), 127 of them had AKI.
The levels of TNF-α, IL-6, IL-8, PCT, ET-1 and IL-10 in the serum of patients in the mild and severe sepsis groups were significantly higher than those in the control group (P<0.05), and the levels in the severe sepsis group were significantly higher than those in the mild sepsis group (P<0.05).
Multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia with severe sepsis in a patient with rheumatoid arthritis (RA), who is predisposed after treatment with tumor necrosis factor inhibitor (TNFI), is a rare severe infection and can be successfully treated with prompt antibiotics.
Principle conclusions: The low producer genotypes of both TNF-α (-308 G/A) and IL-10 (-1082 G/A) polymorphisms could be considered a risk factor for the development of AKI in critically ill patients with severe sepsis, thus management technique implemented for this category should be modulated rescuing this sector of patients from the grave deterioration to acute kidney injury.
Principle conclusions: The low producer genotypes of both TNF-α (-308 G/A) and IL-10 (-1082 G/A) polymorphisms could be considered a risk factor for the development of AKI in critically ill patients with severe sepsis, thus management technique implemented for this category should be modulated rescuing this sector of patients from the grave deterioration to acute kidney injury.
Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis, acute respiratory failure, and hospital mortality among patients with CAP.
The genotype results demonstrated that carriers of the TNF-αrs1800629 A allele had a 4.28-fold higher risk for septic shock (adjusted odds ratio [OR], 4.28; 95% confidence interval [CI], 2.24-8.18; P < .01) compared with severe sepsis, and carriers of the IL-6 rs1800795 C allele had a 2.42-fold higher risk for septic shock (OR, 2.42; 95% CI, 1.08-5.45; P < .01) compared with severe sepsis.
Baseline lHSP72 was higher in SS (p < 0.03), and mHSP72 in SIRS (p < 0.02), compared to H. Only HS induced l/mHSP72/mRNA HSP72; LPS induced IL-6, IL-8, IL-10, and MCP-1.
Since recombinant APC (Drotecogin alfa), originally approved for the treatment of severe sepsis, is not available for human MS studies, we tested the hypothesis that pharmacologic activation of endogenous protein C could likewise improve the outcome of EAE.
Here, ILT4 expression, endotoxin-induced IL-12 and IL-10 production and CD86 expression were investigated in circulating monocytes from 16 patients with severe sepsis and 16 age and sex matched controls.
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.
Moreover, in patients with severe sepsis, individuals with AA+AG genotypes had significantly higher TNF-α serum concentrations than those with GG genotype (P(adj) = 0.02).
Activated protein C (APC) inhibits inflammation and apoptosis in monocytes, and this may partly explain the protective effects of APC treatment in severe sepsis.
These results suggest that the EPCR- and PAR-1-dependent protective effects of APC in severe sepsis may partially be mediated through the inhibition of HMGB1 signaling and that the chimeric thrombin mutant has potential therapeutic utility for severe sepsis.
Therefore, the cytoprotective effects, rather than the anticoagulant effect of APC are postulated to be responsible for the therapeutic benefit of APC in the treatment of severe sepsis.
The monitoring of plasma protein C activity and sufficient administration of activated protein C product could improve the outcome of severe sepsis in children.
Protease activated receptor-1 (PAR1) mediates barrier protective signalling of activated protein C (APC) in human endothelial cells in vitro and may contribute to APC's beneficial effects in patients with severe sepsis.