Lipopolysaccharide-stimulated leukocytes secrete proinflammatory cytokines including tumor necrosis factor-α and interleukin-12. Over-activation of host defense systems may result in severe tissue damage and requires regulation. Granulocyte colony-stimulating factor and interleukin-10 are candidate cytokines for inducing tolerance to lipopolysaccharide re-stimulation. We compared cytokines secreted by lipopolysaccharide-stimulated blood cells from patients who had survived gram negative bacterial pneumonia (
Pseudomonas aeruginosa,
Escherichia coli or
Proteus mirabilis,
n = 26) and age-matched healthy volunteers (
n = 18). Interleukin-12p70 and tumor necrosis factor-α expression was significantly lower in patients (
p = 0.0039 and
p<0.001) compared to healthy controls, while granulocyte colony-stimulating factor production was markedly higher in patients (
p<0.001). Levels of interleukin-10 were comparable. Granulocyte colony-stimulating factor expression was inversely correlated with interleukin-12p70 (R = −0.71,
p<0.001) and tumor necrosis factor-α (R = −0.64,
p<0.001) expression; interleukin-10 showed no significant correlation. In unstimulated leukocytes from patients, cAMP levels were significantly raised (
p = 0.020) and were correlated inversely with interleukin-12p70 levels (R = −0.81,
p<0.001) and directly with granulocyte colony-stimulating factor (R = 0.72,
p = 0.0020), matrix metalloproteinase-9 (R = 0.67,
p = 0.0067) and interleukin-10 (R = 0.54,
p = 0.039) levels. Our results demonstrate that granulocyte colony-stimulating factor production by lipopolysaccharide-stimulated leukocytes is a useful indicator of tolerance induction in surviving pneumonia patients and that measuring cAMP in freshly isolated leukocytes may also be clinically significant.
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