Cortistatin protects mice against lethal endotoxic shock.

Many neuropeptides that regulate activity in the central nervous system (CNS) double as regulators of inflammation. The stress hormone neuropeptide Y, for example, controls both metabolism and heart rate via the CNS and cytokine production by macrophages in the periphery. Cortistatin is no exception—it was originally described as a sleep-promoting hormone produced in response to circadian rhythms, but was recently shown to be produced by activated immune cells.

But the consequences of cortistatin production by immune cells had not been investigated. Gonzalez-Rey and colleagues now show that cortistatin treatment shuts down the synthesis of cytokines and inflammatory mediators by macrophages and protects mice against septic shock. Immune cells produce cortistatin during infection—probably as a means of keeping inflammation in check—but levels of endogenous cortistatin may be too low to shut down cytokine production in the face of a massive bacterial infection.

Cortistatin's close relative somatostatin (which is used to treat certain neuroendocrine cancers) also inhibits cytokine production by macrophages. But somatostatin is not produced by immune cells and, in this model, did not protect against sepsis. If cortistatin, like somatostatin, proves safe in humans, it may be an effective way to treat patients who have septic shock.