title: Lulling immunity, pain, and stress to sleep with cortistatin.
abstract: Cortistatin is a neuropeptide isolated from cortical brain regions, showing high structural homology and sharing many functions with somatostatin. However, cortistatin exerts unique functions in the central nervous and immune systems, including decreasing locomotor activity, inducing sleep-promoting effects, and deactivating inflammatory and T helper (TH )1/TH 17-driven responses in preclinical models of sepsis, arthritis, multiple sclerosis, and colitis. Besides its release by cortical and hippocampal interneurons, cortistatin is produced by macrophages, lymphocytes, and peripheral nociceptive neurons in response to inflammatory stimuli, supporting a physiological role of cortistatin in the immune and nociceptive systems. Cortistatin-deficient mice have been shown to have exacerbated nociceptive responses to neuropathic and inflammatory pain sensitization. However, a paradoxical effect has been observed in studies of immune disorders, in which, despite showing competent inflammatory/autoreactive responses, cortistatin-deficient mice were partially resistant to systemic autoimmunity and inflammation. This unexpected phenotype was associated with elevated circulating glucocorticoids and anxiety-like behavior. These findings support cortistatin as a novel multimodal therapeutic approach to treat autoimmunity and clinical pain and identify it as a key endogenous component of the neuroimmune system related to stress responses.
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, Spanish National Research Council (CSIC), Granada, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gonzalez-Rey
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, Spanish National Research Council (CSIC), Granada, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pedreño
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, Spanish National Research Council (CSIC), Granada, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Delgado-Maroto
authors.affiliation: Oswaldo Cruz Institute, Rio de Janeiro, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Souza-Moreira
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, Spanish National Research Council (CSIC), Granada, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Delgado
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology*; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism*; D009619:Nociceptors / Q000276:immunology; D012890:Sleep / Q000502:physiology*; D013004:Somatostatin / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D009479:Neuropeptides; C099323:cortistatin; D013004:Somatostatin
keywords: autoimmune; inflammation; neuropeptide; pain; stress