Sympathetic activation is associated with increased IL-6, but not CRP in the absence of obesity: lessons from postural tachycardia syndrome and obesity

Abstract

I. Sympathetic activation is associated with increased IL-6, but not CRP in the absence of obesity: lessons from postural tachycardia syndrome and obesity. Am J Physiol Heart Circ Physiol 309: H2098 -H2107, 2015. First published October 9, 2015; doi:10.1152/ajpheart.00409.2015.-Sympathetic activation is thought to contribute to the inflammatory process associated with obesity, which is characterized by elevated circulating C-reactive protein (hsCRP) and interleukin-6 (IL-6). To evaluate whether sympathetic activation is associated with inflammation in the absence of obesity, we studied patients with postural tachycardia syndrome (POTS), a condition characterized by increased sympathetic tone in otherwise healthy individuals. Compared with 23 lean controls, 43 lean female POTS had greater vascular sympathetic modulation (low-frequency blood pressure variability, LFSBP, 3.2 Ϯ 0.4 vs. 5.5 Ϯ 0.6 mmHg 2 , respectively, P ϭ 0.006), lower cardiac parasympathetic modulation (high-frequency heart rate variability, 1,414 Ϯ 398 vs. 369 Ϯ 66 ms 2 , P ϭ 0.001), and increased serum IL-6 (2.33 Ϯ 0.49 vs. 4.15 Ϯ 0.54 pg/ml, P ϭ 0.011), but this was not associated with increases in hsCRP, which was low in both groups (0.69 Ϯ 0.15 vs. 0.82 Ϯ 0.16 mg/l, P ϭ 0.736). To explore the contribution of adiposity to inflammation, we then compared 13 obese female POTS patients and 17 obese female controls to matched lean counterparts (13 POTS and 11 controls). Compared with lean controls, obese controls had increased LFSBP (3.3 Ϯ 0.5 vs. 7.0 Ϯ 1.1 mmHg 2 ; P ϭ 0.016), IL-6 (2.15 Ϯ 0.58 vs. 3.92 Ϯ 0.43 pg/ml; P ϭ 0.030) and hsCRP (0.69 Ϯ 0.20 vs. 3.47 Ϯ 0.72 mg/l; P ϭ 0.001). Obese and lean POTS had similarly high IL-6 but only obese POTS had increased hsCRP (5.76 Ϯ 1.99 mg/l vs. 0.65 Ϯ 0.26; P Ͻ 0.001). In conclusion, sympathetic activation in POTS is associated with increased IL-6 even in the absence of obesity. The coupling between IL-6 and CRP, however, requires increased adiposity, likely through release of IL-6 by visceral fat.

Posttraumatic stress disorder is associated with enhanced interleukin-6 response to mental stress in subjects with a recent myocardial infarction

“…PTSD has been associated with both a decrease in resting cortisol and an increase in corticotropin releasing factor (Baker et al, 2005; Bremner et al, 1997; de Kloet et al, 2008), both of which are associated with higher levels of IL-6 (Swolin-Eide and Ohlsson, 1998; Venihaki et al, 2001). PTSD is also associated with activation of the SAM system (Bremner and Pearce, 2016) which is linked to increased IL-6 (Okamoto et al, 2015). Psychological stress, via SAM system activation, is known to increase binding activity of the nuclear factor-kappa B (NF-kB), an essential transcription factor involved in the activation of immune and inflammatory responses (Bierhaus et al, 2003).…”

Autonomic nervous system activity and inflammation: good ideas, good treatments, or both?

“…Yet, studies translating these concepts from animal to human physiology are scarce. In this issue of the American Journal of Physiology-Heart and Circulatory Physiology, Okamoto et al (10) is exemplary in that regard.…”

“…Okamoto et al (10) investigated the highly complex cross talk between autonomic nervous system, obesity, and inflammation in patients. Obesity is associated with low-grade systemic inflammation and autonomic nervous system imbalance with raised sympathetic and reduced parasympathetic activity.…”

“…The authors hypothesized that the inflammation may be mediated through this autonomic imbalance in persons with obesity. To address this issue, they studied women, who were lean and obese, with and without a diagnosis of the postural tachycardia syndrome (POTS) (10). POTS, which served as human model of sympathetic overactivity and parasympathetic withdrawal, is a chronic condition associated with tachycardia with upright posture.…”

“…Based on the dissociation between circulating interleukin-6, which stimulates hepatic CRP release and CRP concentrations in patients who were lean with POTS, Okamoto et al (10) speculate that the site in which interleukin-6 is produced may be important. Interleukin-6 may have to be produced in visceral adipose tissue directly draining into the portal circulation to elicit CRP release.…”