Autonomic nervous system function predicts the inflammatory response over three years in newly diagnosed ulcerative colitis patients.
BACKGROUND
The autonomic nervous system (ANS) modulates intestinal inflammation in animal models. Human evidence confirming such modulating influence is limited. We aimed to investigate whether ANS function is associated with inflammatory parameters at disease onset, and whether it predicts the evolution of inflammation in patients with ulcerative colitis (UC).


METHODS
We prospectively monitored 51 patients from onset of UC for 3 years. Upon remission of the onset flare, ANS activity was assessed by heart rate variability analysis and compared with healthy controls. Inflammatory parameters in blood, stool, and colonic biopsies obtained at onset and during follow-up visits were analyzed. Generalized linear models were used to test cross-sectional associations between ANS activity and inflammatory parameters at onset; linear mixed models were used to test whether ANS function at onset predicted the evolution of inflammation over the following 3 years.


RESULTS
Sympathovagal balance was different in UC patients compared to healthy controls, and cross-sectional associated with higher levels of systemic (erythrocyte sedimentation rate [ESR], CRP, TNF-α, IFN-γ) and mucosal inflammation (interleukin-8, IFN-γ) at onset. Conversely, a negative cross-sectional association with parasympathetic activity was found for ESR & TNF-α. Longitudinally, parasympathetic activity at onset predicted systemic (ESR, WBC), but not mucosal inflammation during follow-up.


CONCLUSIONS
This study further strengthens the association between the ANS system and intestinal inflammation previously found in animal models and recently in patients with inflammatory bowel disease. These results may have important implications for the pathogenesis and treatment of UC.
Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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V
Gunterberg
Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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M
Simrén
Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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L
Öhman
Department of Clinical Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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P
Friberg
Psychology Faculty, Macquarie University, Sydney, NSW, Australia.
M P
MP
Jones
Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
L
L
Van Oudenhove
Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. hans.strid@vgregion.se.
H
H
Strid
D000328:Adult; D001341:Autonomic Nervous System / Q000502:physiology*; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors
D018836:Inflammation Mediators
autonomic nervous system function; clinical course; inflammation; ulcerative colitis