Autonomic Neuroscience

Available online 13 September 2017

Cardiovascular autonomic regulation, inflammation and pain in rheumatoid arthritis

• Ahmed M. Adlan^a,
• Jet J.C.S. Veldhuijzen van Zanten^a,
• Gregory Y.H. Lip^b,
• Julian F.R. Paton^c,
• George D. Kitas^d,
• James P. Fisher^{a, ,}

https://doi.org/10.1016/j.autneu.2017.09.003

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory condition characterised by reduced heart rate variability (HRV) and increased pain.

Animal studies have demonstrated reciprocal relationships between parasympathetic activity and inflammatory cytokines, however this has not been assessed in humans with RA.

This is the first study to demonstrate that in RA low HRV was associated with increased serum inflammatory cytokine concentrations, and independently associated with increased reported pain.

• In our patients with RA, reductions in HRV were not compounded by the presence of hypertension.

Abstract

Background

Rheumatoid arthritis (RA) is a chronic inflammatory condition characterised by reduced heart rate variability (HRV) of unknown cause. We tested the hypothesis that low HRV, indicative of cardiac autonomic cardiovascular dysfunction, was associated with systemic inflammation and pain. Given the high prevalence of hypertension (HTN) in RA, a condition itself associated with low HRV, we also assessed whether the presence of hypertension further reduced HRV in RA.

Methods

In RA-normotensive (n = 13), RA-HTN (n = 17), normotensive controls (NC; n = 17) and HTN (n = 16) controls, blood pressure and heart rate were recorded. Time and frequency domain measures of HRV along with serological markers of inflammation (high sensitivity C-reactive protein [hs-CRP], tumour necrosis factor-α [TNF-α] and interleukins [IL]) were determined. Reported pain was assessed using a visual analogue scale.

Results

Time (rMSSD, pNN50%) and frequency (high frequency power, low frequency power, total power) domain measures of HRV were lower in the RA, RA-HTN and HTN groups, compared to NC (p = 0.001). However, no significant differences in HRV were noted between the RA, RA-HTN and HTN groups. Inverse associations were found between time and frequency measures of HRV and inflammatory cytokines (IL-6 and IL-10), but were not independent after multivariable analysis. hs-CRP and pain were independently and inversely associated with time domain (rMMSD, pNN50%) parameters of HRV.

Conclusions

These findings suggest that lower HRV is associated with increased inflammation and independently associated with increased reported pain, but not compounded by the presence of HTN in patients with RA.

Corresponding author at: College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

© 2017 Published by Elsevier B.V.

·  Evidence of giant viruses of amoebae in the human gut

Review Article

• Human Microbiome Journal
• Philippe Colson, Sarah Aherfi, Bernard La Scola

Abstract

The study of the gut microbiome and virome has developed dramatically since the beginning of the 21^st century. Nevertheless, giant viruses of amoebae, which are emerging viruses first described in 2003, have been largely neglected in virome investigations because they are bigger than classical viruses and devoid of ribosomal DNA. Dozens of these viruses have been isolated between 2003 and 2016, which were classified in 7 lineages including 3 new recognized virus families. These viruses challenge previous paradigms on viruses and share many characteristics with intra-cellular microbes. We reviewed here findings about the presence of these giant viruses of amoebae in the human gut, whose microbiota has been extensively studied during the last decade. Contrasting with what is currently done for classical viruses, many studies investigating the presence of giant viruses of amoebae have been conducted by culture on amoebae in first intention. To date, a mimivirus and a marseillevirus have been isolated from human feces, which indicates that they can still replicate after a stay in the gut. Besides, sequences related to giant viruses of amoebae have been detected in several metagenomes generated from human feces. Water is a likely source of human exposure to giant viruses of amoebae. The clinical or biological significance of the presence of these viruses in the human gut remains to be determined. Taken together, available findings warrant searching more extensively and systematically for giant viruses of amoebae in the human gut, along with in other body sites.