Plasma concentrations and anti-L-cytokine effects of α-melanocyte stimulating hormone in septic patients

OBJECTIVES:The aim of this research was to investigate endogenous concentrations and anti-cytokine effects of the anti-inflammatory peptide α-melanocyte stimulating hormone (α-MSH) in patients with systemic inflammation. The objectives were to determine the followingchanges over time of plasma α-MSH and relationship with patient outcome, correlation between plasma α-MSH and tumor necrosis factor (TNF)-α plasma concentration and production in whole blood samples, and influences of α-MSH on production of TNF-α and interleukin (IL)-1β in whole blood samples stimulated with lipopolysaccharide (LPS). DESIGN:Prospective, nonrandomized, clinical study. SETTING:Intensive care unit of a university hospital. PATIENTS:A total of 21 patients with sepsis syndrome/septic shock and an equal number of healthy volunteers. INTERVENTIONS:Circulating α-MSH and TNF-α concentrations and TNF-α production in supernatants of LPS (1 ng/mL)-stimulated whole blood were measured repeatedly. To determine whether α-MSH can modulate production of TNF-α and IL-1 β, these cytokines were measured in whole blood samples stimulated with LPS (1 ng/mL) in the presence or absence of concentrations of the peptide. MEASUREMENTS AND MAIN RESULTS:Plasma α-MSH was low in early samples and gradually increased in patients who recovered but not in those who died. There was a negative correlation between plasma concentrations of α-MSH and TNF-α. In blood samples taken at early phases of sepsis syndrome, production of TNF-α was reduced relative to control values; such production increased in patients who recovered but not in those who died. Addition of α-MSH to LPS-stimulated whole blood samples inhibited production of TNF-α and IL-1β in a concentration-dependent manner. CONCLUSIONS:In patients with systemic inflammation, there are substantial changes over time in plasma concentrations of α-MSH that are reduced in early phases of the disease. Reduction of this endogenous modulator of inflammation could be detrimental to the host. Addition of α-MSH to LPS-stimulated blood samples reduces production of cytokines involved in development of septic syndrome. This inhibition by α-MSH, a peptide that is beneficial in treatment of experimental models of sepsis, might therefore be useful to treat sepsis syndrome in humans.