These results indicate that G(Anh)MTetra induces IL-1 beta and IL-6 expression in human monocytes suggesting a possible role for G(Anh)MTetra in the release of cytokines during sepsis.
In marked contrast, with the exception of IL-18 mRNA and IL-6 peptide, there was no increase in serum levels of inflammatory mediators determined both at the onset and during the ongoing states of sepsis.
Because IL-6 is excessively released into the circulation during sepsis and closely correlates with the clinical course, we studied whether this promoter polymorphism has an effect on the incidence and/or outcome of sepsis.
Because of the multiple important biological roles of IL-6, understanding the cellular and molecular mechanisms of mucosal/enterocyte IL-6 production as well as methods to modulate IL-6 production is of clinical importance in the setting of sepsis and other critical illness.
Serum levels of tumour necrosis factor, interleukin (IL)-10, and IL-6 at sepsis onset did not significantly differ between patients carrying wild-type and mutant TLR4.
Other candidate genes for sepsis and septic shock include the interleukin (IL)-1 receptor antagonist gene, the heat shock protein gene, the IL-6 gene, the IL-10 gene, the CD-14 gene, the Toll-like receptor (TLR)-4 gene, and the TLR-2 gene, to name a few.
Among the patients who developed bacterially confirmed septicemia (n = 51 [33%]), there was a significantly higher prevalence of the IL-6 -174 GG genotype than that observed in those who did not develop infection (47% vs 28% for GG: odds ratio [OR]: 2.3; 95% CI: 1.1-4.5).
Candidate single nucleotide polymorphisms (SNPs) within bacterial recognition (TLR4 +896, CD14 -159) and inflammatory response (TNF-alpha -308, IL-1beta -31, IL-6 -174) loci were evaluated for association with increased risk for severe sepsis (sepsis plus organ dysfunction or septic shock) and mortality.
A G-->C polymorphism at position -174 of the IL-6 gene is associated with an adverse outcome in a number of inflammatory diseases, although its association with sepsis as an outcome remains unclear.
With the use of serum IL-6 as a marker for sepsis, infusion of anti-C5aR dramatically reduced serum IL-6 levels, while anti-C5L2 caused a nearly fourfold increase in IL-6 when compared with CLP controls treated with normal IgG.
Blood-culture-proven sepsis occurred in 19% of IL-6-174GG-carriers (n = 157), 26% of IL-6-174GC-carriers (n = 193) and 27% of infants carrying the IL-6-174CC-genotype (n = 67).
In this study, the relationship between the TNF-alpha 308G/A, the IL-6-174 G/C, the PAI-1, the FVL, the EPCR, and the Cathepsin G (Ars 125 Ser) polymorphisms and the development and outcome of sepsis in pediatric patients was studied.
IL-6 gene polymorphisms G-174>C and G-572>C could be the predictors of risk of development and/or the predictors of the severity of sepsis in children.
The aim of the study was therefore to systematically investigate the IL6-174 G/C promoter genotype with regard to the presence of shock in patients with sepsis, the IL6 serum levels, and the ex vivo secretion of IL6, respectively.