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

Anna Catania, Mariagrazia Cutuli, Letizia Garofalo, Lorena Airaghi, Franco Valenza, James M. Lipton, Luciano Gattinoni

Research output: Contribution to journalArticlepeer-review

Abstract

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 following: changes 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.

Original languageEnglish
Pages (from-to)1403-1407
Number of pages5
JournalCritical Care Medicine
Volume28
Issue number5
Publication statusPublished - 2000

Keywords

  • α-melanocyte stimulating hormone
  • Cytokine production
  • Interleukin-1
  • Lipopolysaccharide
  • Sepsis syndrome
  • Septic shock
  • Systemic inflammation
  • Tumor necrosis factor-α
  • Whole blood

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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