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. 2019 Sep 24;14(9):e0221993.
doi: 10.1371/journal.pone.0221993. eCollection 2019.

Identification of inflammatory markers suitable for non-invasive, repeated measurement studies in biobehavioral research: A feasibility study

H M Schenk  1 , S L van Ockenburg  1 , M C Nawijn  2 , P De Jonge  1 , J G M Rosmalen  1
Affiliations

Identification of inflammatory markers suitable for non-invasive, repeated measurement studies in biobehavioral research: A feasibility study

H M Schenk et al. PLoS One. .

Abstract

Introduction: Studying the role of the immune system in the interaction between mental and physical health is challenging. To study individuals with an intensive, longitudinal study design that requires repetitive sampling in their daily life, non-invasive sampling techniques are a necessity. Urine can be collected in a non-invasive way, but this may be demanding for participants and little is known about fluctuation of inflammatory markers in urine over time. The aim of this study was to investigate the feasibility of non-invasive sampling, and to explore intra-individual differences in inflammatory markers in urine.

Materials & methods: Ten healthy individuals collected 24-hour urine for 63 consecutive days. In a pilot analysis, 39 inflammatory markers were examined for detectability in urine, stability over time and under storage conditions, and daily fluctuations. Multiplex analyses were used to quantify levels of eight selected markers: C-reactive protein (CRP), Fractalkine, Interleukin-1 receptor-antagonist (IL-1RA), interferon-α (IFNα), interferon-γ (IFNγ), Interferon gamma-induced protein 10 (IP10), Macrophage inflammatory protein-1β (MIP-1β), and Vascular Endothelial Growth Factor (VEGF). Cross-correlations were calculated between the overnight and 24-hour samples were calculated, to examine whether 24-hour urine could be replaced by the overnight portion for better feasibility. We examined intra- and interindividual differences in the levels of inflammatory markers in urine and the fluctuations thereof.

Results: This study showed that levels of selected inflammatory markers can be detected in urine. Cross-correlation analyses showed that correlations between levels of inflammatory markers in the night portion and the 24-hour urine sample varied widely between individuals. In addition, analyses of time series revealed striking inter- and intra-individual variation in levels of inflammatory markers and their fluctuations.

Conclusion: We show that the assessment of urinary inflammatory markers is feasible in an intensive day-to-day study in healthy individuals. However, 24-hour urine cannot be replaced by an overnight portion to alleviate the protocol burden. Levels of inflammatory markers show substantial variation between and within persons.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Boxplot showing inter- and intra-individual differences of eight inflammatory markers, measured in overnight and day urine, collected during 63 consecutive days in an idiographic study, showing median and interquartile levels of each participant.
CRP = C-reactive protein, IFN = Interferon, IL-1RA = Interleukin-1 receptor antagonist, IP10 = Interferon gamma-induced protein 10, MIP1β = Macrophage Inflammatory Proteins, VEGF = Vascular endothelial growth factor, ng = nanogram, the number on the x-axis represents the individual, n = overnight (gray columns), d = 24-hour urine (white colums).
See this image and copyright information in PMC

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Grants and funding

HMS received a grant from the De Cock-Hadders Foundation (2016-62). The Espria Academy, a health care group in the Netherlands consisting of multiple companies targeted mainly at the elderly population (https://www.espria.nl/), provided funding for the salary of HMS. PdJ received a Dutch National Research council NWO VICI grant (NWO grant 91812607). JGMR received a grant from the Innovation Fund Health Insurances, the Netherlands, grant number 2619. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.