title: Sympathetic activation is associated with increased IL-6, but not CRP in the absence of obesity: lessons from postural tachycardia syndrome and obesity.
abstract: 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 ± 0.4 vs. 5.5 ± 0.6 mmHg(2), respectively, P = 0.006), lower cardiac parasympathetic modulation (high-frequency heart rate variability, 1,414 ± 398 vs. 369 ± 66 ms(2), P = 0.001), and increased serum IL-6 (2.33 ± 0.49 vs. 4.15 ± 0.54 pg/ml, P = 0.011), but this was not associated with increases in hsCRP, which was low in both groups (0.69 ± 0.15 vs. 0.82 ± 0.16 mg/l, P = 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 ± 0.5 vs. 7.0 ± 1.1 mmHg(2); P = 0.016), IL-6 (2.15 ± 0.58 vs. 3.92 ± 0.43 pg/ml; P = 0.030) and hsCRP (0.69 ± 0.20 vs. 3.47 ± 0.72 mg/l; P = 0.001). Obese and lean POTS had similarly high IL-6 but only obese POTS had increased hsCRP (5.76 ± 1.99 mg/l vs. 0.65 ± 0.26; P < 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.
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Luis E
authors.initials: LE
authors.lastname: Okamoto
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University School of Medicine; and.
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gamboa
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Cyndya A
authors.initials: CA
authors.lastname: Shibao
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Amy C
authors.initials: AC
authors.lastname: Arnold
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Emily M
authors.initials: EM
authors.lastname: Garland
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Bonnie K
authors.initials: BK
authors.lastname: Black
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Ginnie
authors.initials: G
authors.lastname: Farley
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Biomedical Engineering, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.affiliation: Vanderbilt Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University School of Medicine; and Italo.biaggioni@vanderbilt.edu.
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
mesh_terms: D050154:Adiposity; D000328:Adult; D001794:Blood Pressure; D001823:Body Composition; D002097:C-Reactive Protein / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology*; D054972:Postural Orthostatic Tachycardia Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D018377:Neurotransmitter Agents; D002097:C-Reactive Protein
keywords: autonomic nervous system; chronic fatigue syndrome; inflammation; obesity; postural tachycardia syndrome