Plasma concentrations and anti-L-cytokine effects of alpha-melanocyte stimulating hormone in septic patients.
OBJECTIVE
The aim of this research was to investigate endogenous concentrations and anti-cytokine effects of the antiinflammatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) in patients with systemic inflammation. The objectives were to determine the following: changes over time of plasma alpha-MSH and relationship with patient outcome, correlation between plasma alpha-MSH and tumor necrosis factor (TNF)-alpha plasma concentration and production in whole blood samples, and influences of alpha-MSH on production of TNF-alpha and interleukin (IL)-1beta in whole blood samples stimulated with lipopolysaccharide (LPS).


METHODS
Prospective, nonrandomized, clinical study.


METHODS
Intensive care unit of a university hospital.


METHODS
A total of 21 patients with sepsis syndrome/septic shock and an equal number of healthy volunteers.


METHODS
Circulating alpha-MSH and TNF-alpha concentrations and TNF-alpha production in supernatants of LPS (1 ng/mL)-stimulated whole blood were measured repeatedly. To determine whether alpha-MSH can modulate production of TNF-alpha and IL-1 beta, these cytokines were measured in whole blood samples stimulated with LPS (1 ng/mL) in the presence or absence of concentrations of the peptide.


RESULTS
Plasma alpha-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 alpha-MSH and TNF-alpha. In blood samples taken at early phases of sepsis syndrome, production of TNF-alpha was reduced relative to control values; such production increased in patients who recovered but not in those who died. Addition of alpha-MSH to LPS-stimulated whole blood samples inhibited production of TNF-alpha and IL-1beta in a concentration-dependent manner.


CONCLUSIONS
In patients with systemic inflammation, there are substantial changes over time in plasma concentrations of alpha-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 alpha-MSH to LPS-stimulated blood samples reduces production of cytokines involved in development of septic syndrome. This inhibition by alpha-MSH, a peptide that is beneficial in treatment of experimental models of sepsis, might therefore be useful to treat sepsis syndrome in humans.
Catania
A
A
Third Division of Internal Medicine, Ospedale Maggiore di Milano IRCCS, Milan, Italy.
Cutuli
M
M
Garofalo
L
L
Airaghi
L
L
Valenza
F
F
Lipton
J M
JM
Gattinoni
L
L
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D000521:alpha-MSH / Q000097:blood*
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH