Specifically, we review the role of IL-10 in human endotoxemia/sepsis and in HIV infection, conditions for which preliminary phase I trials have recently been undertaken.
We report here that inhibition of thymocyte apoptosis by targeted adenovirus-induced thymic expression of human IL-10 reduced blood bacteremia and prevented mortality in sepsis.
We subjected IL-10-deficient (IL-10(-/-)) and wild-type (IL-10(+/+)) mice to CLP and monitored the progression of sepsis, the onset of irreversible shock, and mortality.
IL-10 may represent a future target for immunomodulating patients with the sepsis syndrome or critically ill patients at risk of developing infections.
In addition, in the patients who developed sepsis, interleukin-10 release at admission to the intensive care unit was significantly lower than in patients who did not subsequently develop sepsis (median [range] 1.47 [0.13-6.90] ng/mL compared with 4.93 [0.03-16.80] ng/mL, p = .001).
Interleukin-10 (IL-10) is an anti-inflammatory cytokine and levels have been shown to be highest in those patients who develop sepsis after trauma or surgery.
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.
Considering combinations of genotypes, the TNF-alpha high and IL-10 low producer genotype combination was associated with a approximately 6-fold increased risk of death compared to the TNF-alpha-low and IL-10 intermediate/high producer genotype combination, after adjustment for either APACHE II (P=0.004), MOF score (P=0.004) or sepsis (P=0.006).
In conclusion, this study may indicate that TNF-alpha-308G/A and IL-10-592C/A polymorphisms involved in subsequent activation of cytokine network had a larger effect on clinical outcome in patients with sepsis than TLR4Asp299Gly, Thr399Ile, and CD14-159C/T polymorphisms associated with the initial host-microbial interaction.
The A allele of the -1082 polymorphism in the interleukin-10 gene promoter is associated with sepsis susceptibility, whereas G allele is associated with higher stimulated interleukin-10 production and increased mortality in severe sepsis.
The results demonstrate the advantageous role of de novo IL-10 synthesis in early stages of sepsis and suggest the beneficial impact of gene transfer approach to recombinant protein infusions.
The objectives of this prospective study were to investigate the distribution of IL-10 promoter polymorphisms in a cohort of 308 Chinese Han patients with major trauma, and to identify associations of IL-10 promoter polymorphisms with IL-10 production and incidence of sepsis and MODS.
Distribution of TNF-α(308) genotypes is associated with outcome, IL-10(1082) with type of microorganism and underlying cause of sepsis, and CD14(159) with type of microorganism.
Polymorphisms of IL-1beta/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and TNFalpha/-308 are susceptibility loci for the development of sepsis and organ dysfunction in major trauma patients.
These and other research data clearly demonstrated that the -1082 A/G polymorphism in the IL-10 gene promoter has an important impact on susceptibility of sepsis and sepsis outcome.
Following CASP, Dusp1(-/-) mice had increased serum levels of CCL4, interleukin-10 (IL-10) and IL-6, with differences from wild-type mice being dependent on severity of sepsis.