The splanchnic anti‐inflammatory pathway: could it be the efferent arm of the inflammatory reflex?

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Abstract
New Findings: What is the topic of this review? We review the current literature on the neural reflex termed the ‘inflammatory reflex’ that inhibits an excessive release of inflammatory mediators in response to an immune challenge. What advances does it highlight? The original model proposed that the inflammatory reflex is a vago‐vagal reflex that controls immune function. We posit that, in the endotoxaemic animal model, the vagus nerves do not appear to play a role. The evidence suggests that the efferent motor pathway, termed here the ‘splanchnic anti‐inflammatory pathway’, is purely sympathetic, travelling via the greater splanchnic nerves to regulate the ensuing inflammatory response to immune challenges. Exposure to immune challenges results in the development of inflammation. An insufficient inflammatory response can be life‐threatening, whereas an exaggerated response is also detrimental because it causes tissue damage and, in extreme cases, septic shock that can lead to death. Hence, inflammation must be finely regulated. It is generally accepted that the brain inhibits inflammation induced by an immune challenge in two main ways: humorally, by activating the hypothalamic–pituitary–adrenal axis to release glucocorticoids; and neurally, via a mechanism that has been termed the ‘inflammatory reflex’. The efferent arm of this reflex (the neural‐to‐immune link) was thought to be the ‘cholinergic anti‐inflammatory pathway’. Here, we discuss data that support the hypothesis that the vagus nerves play no role in the control of inflammation in the endotoxaemic animal model. We have shown and posit that it is the greater splanchnic nerves that are activated in response to the immune challenge and that, in turn, drive postganglionic sympathetic neurons to inhibit inflammation.
Funding Information
  • National Health and Medical Research Council (GNT1098887)
  • International Brain Research Organization
  • National Health and Medical Research Council (GNT1079680)

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