The dual role of arginine vasopressin in immune regulation: Balancing immunostimulation and immunosuppression.

Arginine vasopressin (AVP) is a pleiotropic neuroendocrine hormone with diverse physiological functions that have important implications for immune regulation. Although AVP has been reported to exert both immunostimulating and immunosuppressive effects, its actions on immune function are highly context-dependent and arise largely from its established roles in stress physiology, vascular regulation, osmoregulation, and thermoregulation. AVP influences immune activity indirectly through modulation of the hypothalamic-pituitary-adrenal (HPA) axis, blood flow, vascular and lymphatic permeability, fluid balance, and fever responses - all of which shape immune cell trafficking, activation, and inflammatory signaling. In addition, the expression of AVP and its receptors on immunocompetent cells - including T cells, dendritic cells, macrophages, neutrophils, and microglia - supports a role for direct, cell-specific AVP signaling, although the functional consequences of these interactions remain incompletely defined. AVP signaling affects both innate and adaptive immune responses by altering immune cell proliferation, migration, differentiation, and cytokine production in a manner that depends on receptor subtype, cellular content, and physiological state. These immunomodulatory properties are particularly relevant in conditions characterized by neuroendocrine dysregulation, including chronic stress, acquired brain injury, and autoimmune disease, where AVP contributes to cerebral edema, blood-brain barrier disruption, dysregulated HPA axis feedback, and secondary immune activation. This review synthesizes current evidence describing how AVP shapes immune function through integrated neuroendocrine, vascular, and cellular mechanisms, highlights key gaps in mechanistic understanding, and discusses the therapeutic potential - and limitations - of targeting AVP signaling in inflammatory and neuroimmune disease.