Reliability of Serum Biomarkers of Inflammation from Repeated Measures in Healthy Individuals

Biomarkers of low-grade systemic inflammation are used to study the associations of inflammation with chronic diseases, including cancer. However, relatively little is known about the intraindividual variability of most of these measures. Fasting serum samples, collected at baseline and the end of ≥3-week washout periods in a four-diet crossover feeding trial, were used to measure the inflammatory markers high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-8, and soluble TNF receptor (sTNFR) I and II. Participants included 62 men and women for analyses of IL-6 and CRP and 56 for analyses of IL-8, TNF-α, and sTNFRs, aged 20 to 40, who were free of factors known to influence inflammation, for example, chronic disease, medication use, heavy alcohol use, smoking, and obesity (body mass index >30 kg/m(2)). Intraclass correlations (ICC) were estimated using random effects ANOVA, across all four time points (~6 weeks apart). ICCs for TNF-α and sTNFR I and II were very high: ICC = 0.92 [95% confidence interval (CI), 0.89-0.96], 0.92 (95% CI, 0.88-0.95), and 0.90 (95% CI, 0.85-0.94), respectively. ICCs for IL-8 and hsCRP were 0.73 (95% CI, 0.63-0.83) and 0.62 (95% CI, 0.49-0.75), respectively. The ICC for IL-6 was considerably lower, ICC = 0.48 (95% CI, 0.36-0.62). Three measures of IL-6 would be needed to achieve a reliability coefficient (Cronbach α) of 0.75. With the exception of IL-6, reliability of all inflammatory markers in our panel was high. This suggests that a single measure accurately captures the short-term (e.g., 4-6 months) variability within an individual.