Corticotropin-releasing factor family and its receptors: pro-inflammatory or anti-inflammatory targets in the periphery?

The corticotropin-releasing factor (CRF) family of neuropeptides is composed of CRF, urocortin 1 (UCN 1), UCN 2 and UCN 3, which can bind to CRF-binding protein (CRF-BP) and two known receptors, CRFR1 and CRFR2, to perform many pathophysiological functions, including inflammation. In contrast to its anti-inflammatory effect in the central nervous system, the roles of the CRF family and its receptors in the periphery are diverse. However, the biological activities of the CRF family in inflammation are circumstantial and remain controversial. It is suggested that this diverse effects of the CRF family may be due to the different types of CRF receptors, different cells and tissues and even different concentrations of CRF family peptides. Though there are difficulties or limitations in establishing the exact modulatory roles of the CRF family and its receptors in peripheral inflammation, the application of CRF receptor agonists or antagonists to treat inflammatory diseases is being pursued with increasing interest. This review describes the effects and mechanisms of the CRF family and its receptors in inflammation; the possible application of CRF receptor agonists or antagonists in inflammatory diseases or disorders will also be discussed.