Serum levels of the pro-inflammatory cytokine HMGB1 correlate with vagus nerve activity in patients with abdominal aortic aneurysms

Abstract

Supported in part by the National Institute of General Medical Sciences and the National Center for Research Resources. Study objectives: Our recent studies implicated vagus nerve signaling in the regulation of cytokine release. High mobility group box 1 (HMGB1), a newly appreciated proinflammatory cytokine, is released by activated macrophages, and this release is inhibited by cholinergic agonists in vitro. Cholinergic agonists inhibit HMGB1 release in animal models of systemic inflammation, but it is presently unknown whether vagus nerve activity correlates to serum HMGB1 levels in human inflammatory disease. Instantaneous pulse rate variability is a widely used clinical parameter to assess vagus nerve activity in humans. We hypothesize that changes in serum HMGB1 correlate with LF/HF (low-frequency to high-frequency ratios of instantaneous pulse rate variability, indicative of vagus nerve tone). Methods: We performed a prospective observational study on a cohort of 6 abdominal aortic aneurysm patients. Patients were studied sequentially every 4 weeks for 3 months at the General Clinical Research Center. Pulse rate variability was recorded and LF/HF ratios calculated. During each patient visit, serum was obtained for HMGB1 measurements. Results: The results indicate that the serum HMGB1 levels increased as a function of increasing LF/HF ratios. The r2 value was 0.7441 (P<.05). Conclusion: Our results indicate that serum HMGB1 levels inversely correlate with parasympathetic output in agreement with down-modulation of HMGB1 by vagus nerve signaling. Supported in part by the National Institute of General Medical Sciences and the National Center for Research Resources. Study objectives: Our recent studies implicated vagus nerve signaling in the regulation of cytokine release. High mobility group box 1 (HMGB1), a newly appreciated proinflammatory cytokine, is released by activated macrophages, and this release is inhibited by cholinergic agonists in vitro. Cholinergic agonists inhibit HMGB1 release in animal models of systemic inflammation, but it is presently unknown whether vagus nerve activity correlates to serum HMGB1 levels in human inflammatory disease. Instantaneous pulse rate variability is a widely used clinical parameter to assess vagus nerve activity in humans. We hypothesize that changes in serum HMGB1 correlate with LF/HF (low-frequency to high-frequency ratios of instantaneous pulse rate variability, indicative of vagus nerve tone). Methods: We performed a prospective observational study on a cohort of 6 abdominal aortic aneurysm patients. Patients were studied sequentially every 4 weeks for 3 months at the General Clinical Research Center. Pulse rate variability was recorded and LF/HF ratios calculated. During each patient visit, serum was obtained for HMGB1 measurements. Results: The results indicate that the serum HMGB1 levels increased as a function of increasing LF/HF ratios. The r2 value was 0.7441 (P<.05). Conclusion: Our results indicate that serum HMGB1 levels inversely correlate with parasympathetic output in agreement with down-modulation of HMGB1 by vagus nerve signaling.