Stability of individual LPS-induced ex vivo cytokine release in a whole blood assay over a five-year interval

Objective: In epidemiological and clinical studies, whole blood assay (WBA) has been used as a measure to characterize inter-individual differences in the cytokine response of individuals exposed to inflammatory agents, such as endotoxins. Several short-time repeatability studies have shown stable cytokine levels in individuals over periods of days, weeks or months, but little is known about the long-term stability of cytokine reactivity. Methods: We studied cytokine response levels in LPS-stimulated whole blood in a cohort of 193 farmers and agricultural industry workers at two time points with a five-year interval. Results: IL-10 and IL-1 beta responses measured with a five-year time interval showed a weak positive correlation (r = 0.22 and 0.27, respectively), whereas no correlation was observed for TNF alpha (r = 0.06). Cytokine reactivity measured repeatedly at the same time point showed high correlations (IL-10 r = 0.80, IL-1 beta r = 0.53 and TNF alpha r = 0.74), suggesting that the observed weak correlations over time are reflective of actual variations in cytokine reactivity over time. Conclusions: Repeatability of ex vivo cytokine reactivity showed to be differential for the measured cytokines, being more stable for IL-10 and IL-1 beta than for TNF alpha. However, in general, repeatability of ex vivo cytokine reactivity was weak, reflecting that cytokine reactivity can mostly be explained by (short term) intra-individual (immunological) or time varying environmental factors and less by genetic or other time-invariant factors. Therefore, WBA should be regarded as a viable tool to study relationships with current health status and exposure, and only partially as a predictor for a future response.