Reduced CSF Orexin Levels in Rats and Patients with Systemic Inflammation: a Preliminary Study

Objective: Sepsis is a lethal condition characterized by systemic inflammation and multiple organ failure; this condition was initially defined as systemic inflammatory response syndrome (SIRS) due to infection. We previously reported that the hypothalamic neuropeptide orexin improved survival in a murine model of sepsis by mainly acting in the medullary raphe nucleus through orexin type-2 receptors. We hypothesized that orexin treatment enhances recovery from sepsis by reversing the reduction in orexin levels in the cerebrospinal fluid (CSF). We recently reported a case in which CSF orexin levels were reduced in a patient with sepsis. Herein, we attempted to further investigate CSF orexin levels in rats and patients with systemic inflammation. This patient study was a single-center, retrospective observational study.

Results: CSF orexin levels were low in rats with lipopolysaccharide-induced systemic inflammation. We enrolled 14 patients with meningitis/encephalitis. Six patients were diagnosed with SIRS, of whom 5 patients had infections ("sepsis" by the previous definition). CSF orexin levels were low in SIRS patients. The results support the hypothesis that orexin treatment enhances recovery from sepsis by reversing the reduction in CSF orexin levels.