Tone it down: Vagal nerve activity is associated with pro-inflammatory and anti-viral factors in breast cancer – An exploratory study

In response to adverse social-environmental conditions, leukocytes gene expression profile is altered in a pattern recognized as the conserved transcriptional response to adversity (CTRA). This entails the up-regulated expression of pro-inflammatory genes and down-regulated expression of genes involved in type-I interferon (IFN) related anti-viral immunity. In contrast, vagal nerve activity is recognized as a significant anti-inflammatory modulator. In this work, we investigated the association between CTRA and vagal activity indicated by the standard deviation of all NN interval (SDNN), a measure of heart-rate variability, in breast cancer patients awaiting surgery (n = 16). This association was tested both at the molecular leukocyte transcription factor activity level, as well as at the cytokines serum levels. We found an association between higher SDNN and increased interferon (IFN) related anti-viral pathways, both on the leukocyte transcription factor level and serum protein level. Unexpectedly, we also found a positive correlation between higher SDNN and pro-inflammatory transcription factor activity and cytokine serum level, potentially suggesting that increased vagal activity was induced by increased inflammation, in the context of pre-surgical stress and the presence of malignant tissue. Transcription origin analysis (TOA) suggests a role for monocyte and B-cells in the anti-inflammatory and anti-metastatic effects induced by vagal nerve signaling. Larger prospective studies are needed to verify and elaborate on the results from this small cross-sectional study.