Chemokines play a key role in inflammation. They are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types, including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. Here, we investigated a possible neuroendocrine role of the chemokine stromal cell-derived factor 1 (SDF-1)͞CXCL12. We demonstrated the colocalization of SDF-1 and its receptor CXCR4 with arginine vasopressin (AVP) in the magnocellular neurons of the supraoptic nucleus (SON) and the paraventricular hypothalamic nucleus and on AVP projections to the neurohypophysis. Electrophysiological recordings of SON neurons demonstrated that SDF-1 affects the electrical activity of AVP neurons through CXCR4, resulting in changes in AVP release. We observed that SDF-1 can blunt the autoregulation of AVP release in vitro and counteract angiotensin II-induced plasma AVP release in vivo. Furthermore, a short-term physiological increase in AVP release induced by enhanced plasma osmolarity, which was produced by the administration of 1 M NaCl i.p., was similarly blocked by central injection of SDF-1 through CXCR4. A change in water balance by long-term salt loading induced a decrease in both SDF-1 and CXCR4 parallel to that of AVP immunostaining in SON. From these data, we demonstrate that chemokine actions in the brain are not restricted to inflammatory processes. We propose to add to the known autoregulation of AVP on its own neurons, a second autocrine system induced by SDF-1 able to modulate central AVP neuronal activity and release.dehydration ͉ hypothalamic magnocellular neurons ͉ neuroendocrine ͉ neuromodulation ͉ posterior pituitary A rginine vasopressin (AVP) and oxytocin (OT) are synthesized in the magnocellular neurosecretory neurons of the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) and then transported through the median eminence to the posterior lobe of the pituitary gland, where they are secreted into the general blood circulation. AVP is known to be primarily involved in water absorption in the distal nephron of the kidney, thus regulating drinking behavior, whereas the functions of OT during parturition to increase uterine contraction and during suckling have been well described (1).Chemokines are small, secreted molecules (7-14 kDa) with chemoattractant properties whose main accepted role is leukocyte recruitment in inflammatory sites (2, 3). Recent investigations into the possible involvement of chemokines in a number of neurological disorders associated with neuroinflammation have led to the possibility that many chemokines and their respective receptors can be expressed in the brain (4). However, recent data demonstrated that they not only are observed in neuroinflammatory conditions but also are constitutively expressed by different cell types, including neurons in the normal brain (5-7). These data suggest that chemokines may act as modulators of neuronal functions.Among chemokines and chemokine receptors with possible neuromo...

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Chemokines are small secreted proteins that chemoattract and activate immune and non-immune cells both in vivo and in vitro. In addition to their well-established role in the immune system, several recent reports have suggested that chemokines and their receptors may also play a role in the central nervous system (CNS). The best known central action is their ability to act as immuno-inflammatory mediators. Indeed, these proteins regulate leukocyte infiltration in the brain during inflammatory and infectious diseases. However, we and others recently demonstrated that they are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. The goal of this review is to highlight the role of chemokines in the control of neuroendocrine functions. First, we will focus on the expression of chemokines and their receptors in the CNS, with the main spotlight on the neuronal expression in the hypothalamo-pituitary system. Secondly, we will discuss the role -we can now suspect -of chemokines and their receptors in the regulation of neuroendocrine functions. In conclusion, we propose that chemokines can be added to the well-described neuroendocrine regulatory mechanisms, providing an additional fine modulatory tuning system in physiological conditions.