Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction

The nervous and immune systems engage in critical bidirectional communication that influences both physiologic regulation and disease progression. This review discusses the neuroimmune axis and its role in controlling inflammation in AKI and multiorgan dysfunction. Central to this regulation is the inflammatory reflex pathway, which consists of sensory afferent and motor efferent arcs. The cholinergic anti-inflammatory pathway (CAP) suppresses inflammation through vagus nerve activation, norepinephrine release, and α 7 nicotinic acetylcholine receptor signaling in macrophages. Inflammatory mediators activate the afferent vagus nerve, transmitting signals to the brain initiating an anti-inflammatory response. Vagus nerve stimulation and pulsed ultrasound activate the CAP and attenuate inflammation and protect against AKI. Specifically, pulsed ultrasound before kidney ischemia-reperfusion injury reduces inflammation and preserves kidney function in a CAP-dependent manner. Beyond the CAP, other organ systems receive direct vagal innervation, and stimulation of these pathways leads to an anti-inflammatory effect and organ protection. Multiorgan neuroimmune communications, including lung-kidney interactions are discussed, emphasizing their relevance in systemic inflammatory conditions. The role of the inflammatory reflex pathway in sepsis is addressed, emphasizing its potential to modulate the dysregulated immune response contributing to multiorgan failure. Finally, the discussion covers the role of the sympathetic nervous system, particularly renal sympathetic nerve activity, in modulating kidney function and inflammation in AKI. Understanding and targeting these neural circuits may offer novel therapeutic strategies for AKI and related conditions.