The effects of CO2 on cytokine concentrations in endotoxin-stimulated human whole blood

Dai Kimura, Balagangadhar R. Totapally, Andre Raszynski, Cheppail Ramachandran, Dan Torbati

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

OBJECTIVES: Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hypercapnia on blood cytokine production during sepsis is not well understood. We hypothesized that CO2 modulates ex vivo inflammatory cytokine production during endotoxin stimulation. To test this hypothesis, we measured the production of pro- and anti-inflammatory cytokines in endotoxin-stimulated human whole blood cultures under hypercapnic, normocapnic, and hypocapnic conditions. DESIGN: Prospective randomized study. SETTING: Basic research laboratory. SUBJECTS: Ten male and 10 female volunteers. INTERVENTIONS: Venous blood samples, taken from volunteers were cultured at 37°C, under hypocapnic (2% CO2), normocapnic (5% CO2), and hypercapnic (7% CO2) conditions, with and without endotoxin stimulation. After 24 hrs of incubation, each culture's supernatant was analyzed for tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, and interferon-γ concentrations by enzyme-linked immunosorbent assay. Data were analyzed using nonparametric repeated measures of analysis of variance followed by Dunn's multiple comparisons test. Analysis of variance with Bonferroni correction was used to compare gender differences in cytokine concentrations. The Pearson test was used to estimate correlation between hydrogen ion and individual cytokine concentrations. MEASUREMENTS AND MAIN RESULTS: Concentrations of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β and of the anti-inflammatory cytokine interleukin-10 under hypercapnic condition were significantly decreased (p < 0.05, 0.01, and 0.001, respectively) for both genders when compared with either normocapnic or hypocapnic conditions. Concentrations of tumor necrosis factor-α and interleukin-1β were significantly higher in men. In women, concentrations of interleukin-6 were significantly decreased under hypercapnic condition when compared with hypocapnic condition. An inverse relationship was found between hydrogen ion concentration and concentrations of tumor necrosis factor-α and interleukin-10. CONCLUSIONS: Our results are consistent with the hypothesis that CO2 can affect the production of pro- and anti-inflammatory cytokines after ex vivo stimulation with endotoxin.

Original languageEnglish (US)
Pages (from-to)2823-2827
Number of pages5
JournalCritical Care Medicine
Volume36
Issue number10
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Endotoxins
Cytokines
Tumor Necrosis Factor-alpha
Interleukin-1
Interleukin-10
Anti-Inflammatory Agents
Hypercapnia
Volunteers
Interleukin-6
Analysis of Variance
Hypocapnia
Interferons
Protons
Sepsis
Pneumonia
Enzyme-Linked Immunosorbent Assay
Prospective Studies
Research

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

The effects of CO2 on cytokine concentrations in endotoxin-stimulated human whole blood. / Kimura, Dai; Totapally, Balagangadhar R.; Raszynski, Andre; Ramachandran, Cheppail; Torbati, Dan.

In: Critical Care Medicine, Vol. 36, No. 10, 01.01.2008, p. 2823-2827.

Research output: Contribution to journalArticle

Kimura, Dai ; Totapally, Balagangadhar R. ; Raszynski, Andre ; Ramachandran, Cheppail ; Torbati, Dan. / The effects of CO2 on cytokine concentrations in endotoxin-stimulated human whole blood. In: Critical Care Medicine. 2008 ; Vol. 36, No. 10. pp. 2823-2827.
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abstract = "OBJECTIVES: Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hypercapnia on blood cytokine production during sepsis is not well understood. We hypothesized that CO2 modulates ex vivo inflammatory cytokine production during endotoxin stimulation. To test this hypothesis, we measured the production of pro- and anti-inflammatory cytokines in endotoxin-stimulated human whole blood cultures under hypercapnic, normocapnic, and hypocapnic conditions. DESIGN: Prospective randomized study. SETTING: Basic research laboratory. SUBJECTS: Ten male and 10 female volunteers. INTERVENTIONS: Venous blood samples, taken from volunteers were cultured at 37°C, under hypocapnic (2{\%} CO2), normocapnic (5{\%} CO2), and hypercapnic (7{\%} CO2) conditions, with and without endotoxin stimulation. After 24 hrs of incubation, each culture's supernatant was analyzed for tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, and interferon-γ concentrations by enzyme-linked immunosorbent assay. Data were analyzed using nonparametric repeated measures of analysis of variance followed by Dunn's multiple comparisons test. Analysis of variance with Bonferroni correction was used to compare gender differences in cytokine concentrations. The Pearson test was used to estimate correlation between hydrogen ion and individual cytokine concentrations. MEASUREMENTS AND MAIN RESULTS: Concentrations of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β and of the anti-inflammatory cytokine interleukin-10 under hypercapnic condition were significantly decreased (p < 0.05, 0.01, and 0.001, respectively) for both genders when compared with either normocapnic or hypocapnic conditions. Concentrations of tumor necrosis factor-α and interleukin-1β were significantly higher in men. In women, concentrations of interleukin-6 were significantly decreased under hypercapnic condition when compared with hypocapnic condition. An inverse relationship was found between hydrogen ion concentration and concentrations of tumor necrosis factor-α and interleukin-10. CONCLUSIONS: Our results are consistent with the hypothesis that CO2 can affect the production of pro- and anti-inflammatory cytokines after ex vivo stimulation with endotoxin.",
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AU - Kimura, Dai

AU - Totapally, Balagangadhar R.

AU - Raszynski, Andre

AU - Ramachandran, Cheppail

AU - Torbati, Dan

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N2 - OBJECTIVES: Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hypercapnia on blood cytokine production during sepsis is not well understood. We hypothesized that CO2 modulates ex vivo inflammatory cytokine production during endotoxin stimulation. To test this hypothesis, we measured the production of pro- and anti-inflammatory cytokines in endotoxin-stimulated human whole blood cultures under hypercapnic, normocapnic, and hypocapnic conditions. DESIGN: Prospective randomized study. SETTING: Basic research laboratory. SUBJECTS: Ten male and 10 female volunteers. INTERVENTIONS: Venous blood samples, taken from volunteers were cultured at 37°C, under hypocapnic (2% CO2), normocapnic (5% CO2), and hypercapnic (7% CO2) conditions, with and without endotoxin stimulation. After 24 hrs of incubation, each culture's supernatant was analyzed for tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, and interferon-γ concentrations by enzyme-linked immunosorbent assay. Data were analyzed using nonparametric repeated measures of analysis of variance followed by Dunn's multiple comparisons test. Analysis of variance with Bonferroni correction was used to compare gender differences in cytokine concentrations. The Pearson test was used to estimate correlation between hydrogen ion and individual cytokine concentrations. MEASUREMENTS AND MAIN RESULTS: Concentrations of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β and of the anti-inflammatory cytokine interleukin-10 under hypercapnic condition were significantly decreased (p < 0.05, 0.01, and 0.001, respectively) for both genders when compared with either normocapnic or hypocapnic conditions. Concentrations of tumor necrosis factor-α and interleukin-1β were significantly higher in men. In women, concentrations of interleukin-6 were significantly decreased under hypercapnic condition when compared with hypocapnic condition. An inverse relationship was found between hydrogen ion concentration and concentrations of tumor necrosis factor-α and interleukin-10. CONCLUSIONS: Our results are consistent with the hypothesis that CO2 can affect the production of pro- and anti-inflammatory cytokines after ex vivo stimulation with endotoxin.

AB - OBJECTIVES: Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hypercapnia on blood cytokine production during sepsis is not well understood. We hypothesized that CO2 modulates ex vivo inflammatory cytokine production during endotoxin stimulation. To test this hypothesis, we measured the production of pro- and anti-inflammatory cytokines in endotoxin-stimulated human whole blood cultures under hypercapnic, normocapnic, and hypocapnic conditions. DESIGN: Prospective randomized study. SETTING: Basic research laboratory. SUBJECTS: Ten male and 10 female volunteers. INTERVENTIONS: Venous blood samples, taken from volunteers were cultured at 37°C, under hypocapnic (2% CO2), normocapnic (5% CO2), and hypercapnic (7% CO2) conditions, with and without endotoxin stimulation. After 24 hrs of incubation, each culture's supernatant was analyzed for tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, and interferon-γ concentrations by enzyme-linked immunosorbent assay. Data were analyzed using nonparametric repeated measures of analysis of variance followed by Dunn's multiple comparisons test. Analysis of variance with Bonferroni correction was used to compare gender differences in cytokine concentrations. The Pearson test was used to estimate correlation between hydrogen ion and individual cytokine concentrations. MEASUREMENTS AND MAIN RESULTS: Concentrations of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β and of the anti-inflammatory cytokine interleukin-10 under hypercapnic condition were significantly decreased (p < 0.05, 0.01, and 0.001, respectively) for both genders when compared with either normocapnic or hypocapnic conditions. Concentrations of tumor necrosis factor-α and interleukin-1β were significantly higher in men. In women, concentrations of interleukin-6 were significantly decreased under hypercapnic condition when compared with hypocapnic condition. An inverse relationship was found between hydrogen ion concentration and concentrations of tumor necrosis factor-α and interleukin-10. CONCLUSIONS: Our results are consistent with the hypothesis that CO2 can affect the production of pro- and anti-inflammatory cytokines after ex vivo stimulation with endotoxin.

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