Endotoxin Stimulated Interleukin-10 Production is Enhanced by Adenosine. Possible Key to Septic Shock Associated Immune Deficiency?

Abstract

The aim of this bench study was to investigate whether adenosine influences secretion of interleukin-10 (IL-10) in human whole blood culture stimulated with lipopolysaccharide. Whole blood from healthy human volunteers was mixed ex vivo in 1:1 ratio with RPMI 1640 culture medium and subsequently cultured at 37°C with or without adenosine (total of 120 μM added in four aliquots over two hours) in the presence or absence of 100 ng/ml lipopolysaccharide for four and eight hours, respectively. There was only a minimal IL-10 production after four hours of culture regardless of the experimental conditions. However, lipopolysaccharide stimulated whole blood cultures with added adenosine released large amounts of IL-10 after eight hours. The response was similar whether adenosine was added before (5.99 pg/ml/106 leucocytes) or after (10.35 pg/ml/106 leucocytes) stimulation with lipopolysaccharide and inter-individual variation was present. In conclusion adenosine enhances lipopolysaccharide stimulated IL-10 production in whole human blood and may contribute to the IL-10 mediated immune dysfunction in sepsis.