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The vagus nerve and the inflammatory reflex—linking immunity and metabolism


The vagus nerve has an important role in regulation of metabolic homeostasis, and efferent vagus nerve-mediated cholinergic signalling controls immune function and proinflammatory responses via the inflammatory reflex. Dysregulation of metabolism and immune function in obesity are associated with chronic inflammation, a critical step in the pathogenesis of insulin resistance and type 2 diabetes mellitus. Cholinergic mechanisms within the inflammatory reflex have, in the past 2 years, been implicated in attenuating obesity-related inflammation and metabolic complications. This knowledge has led to the exploration of novel therapeutic approaches in the treatment of obesity-related disorders.

Key Points

  • The inflammatory reflex is a physiological mechanism through which the vagus nerve regulates immune function and inhibits excessive proinflammatory cytokine production

  • Vagus nerve signalling has an important role in the regulation of feeding behaviour and metabolic homeostasis

  • Disruption of metabolic and immune regulation in obesity results in inflammation, which mediates insulin resistance and the development of type 2 diabetes mellitus as well as other debilitating and life-threatening conditions

  • Activation of cholinergic signalling in the efferent arm of the inflammatory reflex alleviates obesity-associated inflammation and metabolic derangements

  • The inflammatory reflex can potentially be exploited for treatment of the metabolic syndrome, type 2 diabetes mellitus and other obesity-driven disorders

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Figure 1: The functional anatomy of the inflammatory reflex.
Figure 2: Molecular mechanisms of cholinergic control of inflammation.
Figure 3: The role of the vagus nerve in metabolic regulation.
Figure 4: Possible therapies based on cholinergic-based approaches for the treatment of obesity-driven disorders.


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The authors' research work is supported in part by grants from the National Institute of General Medical Sciences, NIH. The authors thank Peder S. Olofsson for critical reading of the manuscript.

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Both authors contributed equally to researching data for the article, writing the manuscript, discussions of the content, and review or editing of the manuscript before submission.

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Correspondence to Valentin A. Pavlov.

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Competing interests

K. J. Tracey is a cofounder of and consultant to SetPoint Medical, Inc. Both authors are inventors on the following patent: “Cholinesterase inhibitors for treating inflammation” (patent number 8,003,632). K. J. Tracey also is an inventor of other patents related to the content of this review: “Treatment of inflammation using α7 receptor-binding cholinergic agonists” (patent number 7,785,808); “Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation” (patent number 6,838,471).

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Pavlov, V., Tracey, K. The vagus nerve and the inflammatory reflex—linking immunity and metabolism. Nat Rev Endocrinol 8, 743–754 (2012).

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