The vasopressin system as an immunoneuroendocrine therapeutic target in inflammatory conditions.

Arginine vasopressin (AVP), a nonapeptide produced mainly in hypothalamic neurons, is known for regulating osmotic balance and blood vessel tone. Recent evidence shows it also plays key roles in the immunoneuroendocrine axis, reproduction, and cellular stress. This review explores its role as an immune regulator involving hypothalamic signals, organ responses, and inflammation. We cover AVP's structure, receptor types (V1a, V1b, V2), pharmacological analogs, and their interactions with cytokines and immune cells. Experimental and translational data indicate that AVP exerts context-dependent effects on inflammation, either amplifying or constraining immune activation, depending on receptor engagement, the signaling milieu, and the tissue microenvironment. V1a receptor-mediated vasoconstriction, endothelial dysfunction, and pro-inflammatory signaling (including NF-κB and inflammasome activation) can contribute to microcirculatory impairment and organ injury in pathological states, whereas V2 receptor activation may mediate anti-inflammatory and cytoprotective effects in selected settings. These actions are not fixed to individual receptor subtypes but are shaped by dose, disease stage, and host neuroendocrine status. Receptor-specific modulation influences cytokine profiles, leukocyte recruitment, and hypothalamic-pituitary-adrenal feedback, and has been examined in sepsis, ischemia-reperfusion injury, and autoimmune or neuroinflammatory models. Collectively, current evidence supports the AVP system as a mechanistically relevant but still largely preclinical target in inflammation-driven diseases. Potential therapeutic applications of selective AVP agonists and antagonists should therefore be considered hypothesis-generating. These applications will require rigorous validation in well-designed experimental and clinical studies before any firm recommendations can be made.