The Multi-faceted Profile of Corticotropin-releasing Factor (CRF) Family of Neuropeptides and of their Receptors on the Paracrine/Local Regulation of the Inflammatory Response

The corticotropin releasing factor (CRF) family of neuropeptides, CRF and the Urocortins, and their receptors are present not only within the central nervous system but also in the periphery at various locations and at the sites of inflammation where they influence its progress in a complex local / paracrine manner. These neuropeptides are either produced locally, by components of the inflammatory response or they may reach the inflammation sites via postganglionic sympathetic and sensory afferent nerve transport. The local effects of the CRF family of neuropeptides can be either pro- or anti-inflammatory depending on concentration of each type of neuropeptide present and the ratio of the local expression of their receptors i.e. type 1 (CRF1R) and type 2 (CRF2R). It now appears that most immune cells taking part in the inflammatory process express the CRF1R and CRF2R and thus represent targets of CRF neuropeptides. Indeed, mast cells, monocytes / macrophages, neutrophils and other types of immune cells express both types of the CRF receptors. In addition to their role in the pathophysiology of inflammation, CRF and its receptors also exert modulatory effects on inflammatory pain. Finally, it now appears that the CRF system is also present in adipose tissue and may play a crucial role in the development of the chronic low grade inflammation, which is characteristic of obesity.