期刊名称:Journal of Clinical Biochemistry and Nutrition
印刷版ISSN:0912-0009
电子版ISSN:1880-5086
出版年度:2011
卷号:48
期号:2
页码:134-141
DOI:10.3164/jcbn.10-72
出版社:The Society for Free Radical Research Japan
摘要: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.