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

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.