cortistatin-14 and Immune-System-Diseases

Somatostatin receptors (sst), somatostatin (SS) and cortistatin (CST) are widely expressed in the various systems in the human and rodent organisms and are "responsible" for maintaining homeostasis, which is essential for survival. Because of their broad expression pattern sst, SS and CST interactions may play regulatory roles in both physiology and pathophysiology in mammalian organisms. SS analogue treatment strategies as well as the use of SS analogues for diagnostic purposes have been established in diseases of different origins. This review focuses on the currently determined role for SS analogues in today's clinical practice and the potential clinical prospects for SS, CST and sst interactions in the future, with a focus on neuroendocrine and non-neuroendocrine tumours and immune-mediated diseases. Moreover, the role of new SS analogues and new insights in sst physiology will be discussed.

Topics: Antineoplastic Agents, Hormonal; Endocrine Gland Neoplasms; Endocrine System Diseases; Humans; Immune System; Immune System Diseases; Neoplasms; Neuropeptides; Neurosecretory Systems; Radionuclide Imaging; Receptors, Somatostatin; Somatostatin

Hormones and neuropeptides may influence the activities of lymphoid organs and cells via endocrine and local autocrine/paracrine pathways. A paradigm of the interactions between the neuroendocrine and immune system is sophisticatedly represented in the thymus. Indeed, receptors for these molecules are heterogeneously expressed in all subsets of thymic cells, and the communications are tuned by feedback circuitries. Herein, we focus on somatostatin (SS), a ubiquitous peptide that regulates several physiological cell processes and acts via five specific receptor (SSR) subtypes (sst(1-5)). Neuronal and accessory cells, so-called neuroendocrine cells, and immune cells, heterogeneously express SSRs. The functional characterization of SSRs in vivo by nuclear medicine techniques opened a complex scenario on the significance of SS/SSR pathway in immune system and related diseases. Several studies have established that SSR scintigraphy may benefit patients with chronic inflammatory and granulomatous diseases, as well as lymphoproliferative diseases. The results are sufficiently promising to warrant larger studies aimed at defining the exact role of these techniques. The development of SS analogs with antisecretory and antiproliferative effects has radically changed the management of neuroendocrine tumors. Moreover, very important recent findings, emerging from in vitro studies on SSR physiology in immune cells, will certainly expand the potential applications of SS analogs for in vivo diagnostic and therapeutic options. Indeed, the anti-inflammatory and analgesic effects of these drugs remain incompletely understood, but may prove useful in a number of autoimmune diseases. Because SS expression is absent in different immune tissues where SSRs are present, the existence of another ligand was hypothesized. In fact, it has been recently demonstrated that human lymphoid tissues and immune cells may express cortistatin (CST). CST is known to bind SSRs and shares many pharmacological and functional properties with SS. However, CST has also properties distinct from SS, and the higher expression of CST in immune cells supports the hypothesis that CST rather than SS may act as a potential endogenous ligand for SSRs in the human immune system.

Topics: Animals; Humans; Immune System Diseases; Lymphoid Tissue; Neuropeptides; Neurosecretory Systems; Receptors, Somatostatin; Somatostatin