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.