Cortistatin-14

Cortistatin-14

Evidence & Status

  • Preliminary / Experimental
  • Preliminary

At a Glance

A neuropeptide produced in the brain that is structurally similar to somatostatin but activates additional receptors, giving it a distinct immunomodulatory and anti-inflammatory profile. Studied in models of inflammatory diseases, sepsis, and autoimmune conditions.

Plain English

Researchers study Cortistatin-14 because, despite its structural resemblance to somatostatin, it has distinct biological effects — particularly in regulating immune responses. Scientists are interested in its ability to influence macrophage behavior, reduce inflammation through multiple pathways, and potentially protect against the immune dysregulation that occurs in conditions like sepsis. Research is primarily preclinical, with animal models of inflammatory bowel disease, rheumatoid arthritis, and sepsis representing the main areas of investigation.

Overview

A cyclic neuropeptide produced in the cerebral cortex and hippocampus that shares 11 of 14 amino acids with somatostatin-14 and binds all five somatostatin receptors with similar affinity. Despite this structural similarity, cortistatin activates additional receptors not activated by somatostatin — including MCHR1 (melanin-concentrating hormone receptor 1) and MrgX2. This distinct receptor profile translates into unique immunomodulatory and anti-inflammatory properties that differentiate it from the purely neuroendocrine actions of somatostatin analogs.

Research Summary

Cortistatin-14 is a cyclic neuropeptide first isolated from rat cortex, sharing 11 of 14 residues with somatostatin-14 while retaining a distinct receptor profile that includes additional targets such as MCHR1. Preclinical work has examined immune and inflammatory signaling, but those findings do not establish a therapy. Direct human evidence is limited to small endocrine research exposures involving intravenous cortistatin-14 and its interaction with related secretagogues; these studies were not therapeutic efficacy trials. Cortistatin-14 remains investigational, and human dosing, pharmacokinetics, and safety are not established.

Research Areas

  • Immune regulation and anti-inflammation
  • Macrophage polarization
  • Sepsis
  • Inflammatory bowel disease
  • Rheumatoid arthritis
  • Neuroinflammation

Safety & Risks

Serious Risks

  • Insufficient human safety data
  • Immune suppression concerns in infection settings
  • Broad receptor engagement (somatostatin + MCHR1 + MrgX2)

Reported Side Effects

  • Not well-characterized in humans
  • Similar to somatostatin-like effects at high doses (GI motility, glucose effects)
United States
Research only
United Kingdom
Research only
Australia
Research only
Canada
Research only

Citations & Sources