Intra-individual variability over time in serum cytokine levels among participants in the prostate, lung, colorectal, and ovarian cancer screening Trial.

Authors

Hofmann JN, Yu K, Bagni RK, Lan Q, Rothman N, Purdue MP

Affiliations

• Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7240, United States. hofmannjn@mail.nih.gov

Abstract

BACKGROUND: Serum measurements of cytokines, mediators of various B and T cell activities, are important markers of inflammation and immune dysregulation. We assessed the reproducibility of serum cytokine measurements over a five-year period among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).

METHODS: Levels of 13 cytokines [interleukin (IL) 1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, interferon-gamma (IFNγ), granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNFα)] in stored sera from three collections (study baseline,+1 year, and+5 years) among 28 randomly selected PLCO participants were measured using a high-sensitivity Luminex xMap-based multiplex panel. Within- and between-subject components of variance were estimated from random effects models and were used to calculate the coefficient of variation (CV) and intraclass correlation coefficient (ICC) for analytes with <30% of samples below the limit of detection (LOD). Spearman correlation coefficients between measurements of the same analyte over time and between analytes were also calculated.

RESULTS: Among the six cytokines with <30% of samples below the LOD, we observed excellent reproducibility for IL-6, IL-7, IL-13, and TNFα (ICC≥0.73), and fair to good reproducibility for IL-8 (ICC=0.55) and IL-10 (ICC=0.60). Spearman correlation coefficients comparing paired measurements of each cytokine at baseline and at +5 years were high (ρ≥0.74) with the exception of IL-10 (ρ=0.44).

CONCLUSIONS: These results suggest that measurements of most of the cytokines evaluated in this study were highly reproducible over five-year periods.