Skip to main content

Interplay between the innate immune response and heart rate variability in healthy human volunteers

Introduction

The autonomic nervous system (ANS) and innate immunity are intimately linked. Heart rate variability (HRV) analysis is a widely employed method to assess cardiac ANS activity, and changes in HRV indices may correlate with inflammatory markers. Here, we investigated whether baseline HRV predicts the innate immune response. Second, we investigated whether the magnitude of the inflammatory response correlated with HRV alterations.

Methods

Forty healthy volunteers received a single intravenous bolus of 2 ng/kg endotoxin (lipopolysaccharide (LPS), derived from Escherichia coli O:113). Of these, 12 healthy volunteers were administered LPS again 2 weeks later. HRV was determined at baseline (just prior to LPS administration) and hourly thereafter until 8 hours post LPS. Plasma cytokine levels were determined at various time points.

Results

Baseline HRV indices did not correlate with the magnitude of the LPS-induced inflammatory response. Despite large alterations in HRV following LPS administration, the extent of the inflammatory response did not correlate with the magnitude of HRV changes. In subjects that were administered LPS twice, inflammatory cytokines were markedly attenuated following the second LPS administration, while LPS-induced HRV alterations were similar. See Figure 1.

Figure 1
figure1

Association between basal HRV indices (calculated at t = 0, just prior to LPS administration) and area under curve of the LPS-induced proinflammatory cytokine response (TNFα and IL-6, log pg/ml/hour) of 40 subjects. ms, milliseconds; AU, arbitrary units. Solid and dashed lines, TNFα and IL-6 regression lines, respectively. Pearson correlation coefficients (none statistically significant) indicated.

Conclusions

HRV indices do not predict the innate immune response in a standardized model of systemic inflammation. The innate immune response results in HRV changes; however, no correlations with inflammatory cytokines were observed. These findings suggest that cardiac ANS activity may not reflect ANS outflow to other organs involved in the innate immune response. Furthermore, the magnitude of endotoxemia-related HRV changes does not reflect the extent of the inflammatory response.

Author information

Affiliations

Authors

Corresponding author

Correspondence to M Kox.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Kox, M., Ramakers, B., Pompe, J. et al. Interplay between the innate immune response and heart rate variability in healthy human volunteers. Crit Care 15, P258 (2011). https://doi.org/10.1186/cc9678

Download citation

Keywords

  • Inflammatory Response
  • Heart Rate Variability
  • Inflammatory Cytokine
  • Autonomic Nervous System
  • Innate Immune Response