Neuroendocrine-immune interaction: regulation of inflammation via G-protein coupled receptors

Neuroendocrine- and immune systems interact in a bi-directional fashion to communicate the status of pathogen recognition to the brain and the immune response is influenced by physiological changes. The network of ligands and their receptors involved includes cytokines and chemokines, corticosteroids, classical pituitary hormones, catecholamines and neuropeptides (e.g. opioids), as well as neural pathways. We studied the role of opioid, adrenergic and melatonin G-protein coupled receptors (GPCR) on carp (Cyprinus carpio) leucocytes. Ligand interaction by morphine and adrenaline both in vitro and in vivo resulted in considerable decrease of chemotaxis and expression of CXC chemokines and chemokine CXC receptors. These effects may have substantial influence on the process of inflammation, the efficacy of which is crucial for an effective immune response. Both opioid receptors and chemokine receptors are G-protein coupled receptors (GPCRs), and were classically assumed to function as monomers. This paradigm is now challenged by the emerging concept of homo- and hetero dimerization which may represent the native form of many receptors. G-protein coupling, downstream signaling and regulatory processes such as receptor internalization are largely influenced by the dimeric nature. The true functional importance of GPCR interactions remains enigmatic, but it certainly has implications with respect to the specificity of currently used medications. This review focuses on the important function of chemokine GPCRs during inflammation and the potential neuroendocrine modulation of this process through "neuroendocrine" GPCRs.