Raised interleukin-10 is an indicator of poor outcome and enhanced systemic inflammation in patients with acute coronary syndrome

Abstract

Objectives: To re-evaluate the relation between plasma interleukin-10 (IL-10) concentration at hospital admission and outcome and to investigate the impact of single nucleotide polymorphisms (SNP) in the IL-10 gene in patients with non-ST elevation acute coronary syndrome (ACS).

Design: Determination of IL-10 plasma concentrations and genotyping of SNPs in the IL-10 gene in a prospective trial of patients with ACS and in a group of healthy controls.

Patients: 3179 patients in the Fragmin and fast revascularisation during InStability in Coronary artery disease II (FRISC II) trial and 393 healthy controls.

Main outcome measures: Mortality and incidence of myocardial infarction (MI) at 12 months.

Results: The median and interquartile ranges of IL-10 were 0.8 (0.5-1.0) pg/ml in healthy controls and 1.1 (0.7-1.9) pg/ml in patients (p<0.001). In patients, IL-10 predicted a crude risk increase of death/MI, with the highest risk observed in the fourth quartile (adjusted odds ratio 1.7 (95% confidence interval 1.2 to 2.3)). Adjustment for common risk indicators, including C-reactive protein and interleukin-6, weakened the association to a non-significant level. The 1170 CC genotype weakly predicted increased plasma concentrations of IL-10 in patients (p = 0.04) and in controls (p = 0.03), which was consistent with the modest association of this variant with coronary disease (p = 0.01).

Conclusion: In contrast with some previous reports, we conclude that IL-10 reflects a proinflammatory state in patients with ACS and we therefore suggest that IL-10 is as effective a biomarker for the risk prediction of future cardiovascular events as other markers of systemic inflammation.

Figure 1. The IL-10 gene and the SNPs genotyped in the present study. The SNPs are indicated as position major>minor allele shift. Open boxes represent exons and shaded boxes represent untranslated regions.

Figure 2. Box plot of IL-10 plasma concentrations in healthy controls and patients with acute coronary syndrome.

Figure 3. Hours between study randomisation and blood sampling.

Figure 4. Probability of death and myocardial infarction (MI) according to IL-10 quartiles. (A) Kaplan-Meier estimate of the cumulative 12-month probability of death. (B) Kaplan-Meier estimate of the 12-month cumulative probability of MI.

Figure 5. Plasma concentrations of interleukin-10 and C-reactive protein in patients and healthy controls according to 1170 C>T genotypes. The box plot represents medians, interquartile ranges and 10th–90th percentiles. *p<0.05.