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Relationship between the cAMP levels in leukocytes and the cytokine balance in patients surviving gram negative bacterial pneumonia.

Matsumoto T, Hayamizu K, Marubayashi S, Shimizu K, Hamamoto A, Yamaguchi T, Hashizume J, Onabe T, Asahara T, Ohdan H - J Clin Biochem Nutr (2011)

Bottom Line: Over-activation of host defense systems may result in severe tissue damage and requires regulation.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).Levels of interleukin-10 were comparable.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 734-8551, Japan.

ABSTRACT
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.

No MeSH data available.


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Relationship between intracellular cAMP levels and cytokines secreted by LPS-stimulated leukocytes. (A) cAMP level in freshly isolated leukocytes from age-matched healthy volunteers (n = 9) and patients with gram negative bacterial pneumonia (n = 6) were compared statistically. (B) cAMP levels and the concentrations of cytokines and MMP-9 from blood cells stimulated with LPS in vitro were plotted as X and Y and fitted to an exponential distribution in which Y is proportional to ebx. Correlation coefficients (R) between X and log Y and the slope of the regression line ((log Y)/X) (b) were calculated. Samples were from patients (n = 6, closed triangle) or age-matched healthy volunteers (n = 9, open square).
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Figure 5: Relationship between intracellular cAMP levels and cytokines secreted by LPS-stimulated leukocytes. (A) cAMP level in freshly isolated leukocytes from age-matched healthy volunteers (n = 9) and patients with gram negative bacterial pneumonia (n = 6) were compared statistically. (B) cAMP levels and the concentrations of cytokines and MMP-9 from blood cells stimulated with LPS in vitro were plotted as X and Y and fitted to an exponential distribution in which Y is proportional to ebx. Correlation coefficients (R) between X and log Y and the slope of the regression line ((log Y)/X) (b) were calculated. Samples were from patients (n = 6, closed triangle) or age-matched healthy volunteers (n = 9, open square).

Mentions: We next quantified and analyzed the cAMP content of freshly isolated leukocytes. As shown in Fig. 5A, cAMP levels were significantly higher in patients (p = 0.020) compared to healthy volunteers. Fig. 5B shows the relationship between cAMP (X) and cytokine production (Y), fitted to exponential curves in which Y is proportional to ebX, where e is the base of the natural logarithm and b is a constant. The levels of cAMP were inversely correlated with IL-12p70 production (R = −0.81, p<0.001, b = −0.13) and directly correlated with G-CSF (R = 0.72, p = 0.0020, b = 0.089), MMP-9 (R = 0.67, p = 0.0067, b = 0.041) and IL-10 (R = 0.54, p = 0.039, b = 0.049) production. These results helped to explain why the relationship between cytokine production follows a power-law relationship. No statistically significant correlation was detected between cAMP and TNF-α levels in this experiment. In particular, the production of IL-12p70 and G-CSF showed similar degrees of sensitivity, as expressed by the values of b, to intracellular cAMP, which explains the inverse relationship seen between IL-12p70 and G-CSF production seen in Fig. 3.


Relationship between the cAMP levels in leukocytes and the cytokine balance in patients surviving gram negative bacterial pneumonia.

Matsumoto T, Hayamizu K, Marubayashi S, Shimizu K, Hamamoto A, Yamaguchi T, Hashizume J, Onabe T, Asahara T, Ohdan H - J Clin Biochem Nutr (2011)

Relationship between intracellular cAMP levels and cytokines secreted by LPS-stimulated leukocytes. (A) cAMP level in freshly isolated leukocytes from age-matched healthy volunteers (n = 9) and patients with gram negative bacterial pneumonia (n = 6) were compared statistically. (B) cAMP levels and the concentrations of cytokines and MMP-9 from blood cells stimulated with LPS in vitro were plotted as X and Y and fitted to an exponential distribution in which Y is proportional to ebx. Correlation coefficients (R) between X and log Y and the slope of the regression line ((log Y)/X) (b) were calculated. Samples were from patients (n = 6, closed triangle) or age-matched healthy volunteers (n = 9, open square).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 5: Relationship between intracellular cAMP levels and cytokines secreted by LPS-stimulated leukocytes. (A) cAMP level in freshly isolated leukocytes from age-matched healthy volunteers (n = 9) and patients with gram negative bacterial pneumonia (n = 6) were compared statistically. (B) cAMP levels and the concentrations of cytokines and MMP-9 from blood cells stimulated with LPS in vitro were plotted as X and Y and fitted to an exponential distribution in which Y is proportional to ebx. Correlation coefficients (R) between X and log Y and the slope of the regression line ((log Y)/X) (b) were calculated. Samples were from patients (n = 6, closed triangle) or age-matched healthy volunteers (n = 9, open square).
Mentions: We next quantified and analyzed the cAMP content of freshly isolated leukocytes. As shown in Fig. 5A, cAMP levels were significantly higher in patients (p = 0.020) compared to healthy volunteers. Fig. 5B shows the relationship between cAMP (X) and cytokine production (Y), fitted to exponential curves in which Y is proportional to ebX, where e is the base of the natural logarithm and b is a constant. The levels of cAMP were inversely correlated with IL-12p70 production (R = −0.81, p<0.001, b = −0.13) and directly correlated with G-CSF (R = 0.72, p = 0.0020, b = 0.089), MMP-9 (R = 0.67, p = 0.0067, b = 0.041) and IL-10 (R = 0.54, p = 0.039, b = 0.049) production. These results helped to explain why the relationship between cytokine production follows a power-law relationship. No statistically significant correlation was detected between cAMP and TNF-α levels in this experiment. In particular, the production of IL-12p70 and G-CSF showed similar degrees of sensitivity, as expressed by the values of b, to intracellular cAMP, which explains the inverse relationship seen between IL-12p70 and G-CSF production seen in Fig. 3.

Bottom Line: Over-activation of host defense systems may result in severe tissue damage and requires regulation.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).Levels of interleukin-10 were comparable.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 734-8551, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus