Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock

Tacla Sfeir, Dhanonjoy C. Saha, Mark Astiz, Eric C. Rackow

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Objectives: The purpose of this study was to examine the pattern of tumor necrosis factor (TNF)-α and interleukin (IL)-10 release in endotoxin-stimulated septic monocytes and to determine the role of IL-10 and transforming growth factor (TGF)-β in monocyte hyporesponsiveness during septic shock. Design: Monocytes isolated from ten healthy controls and ten patients with septic shock were incubated with endotoxin and cytokine release was assessed. Next, normal monocytes were incubated with either normal or septic serum and stimulated with endotoxin. Finally, normal monocytes were incubated with septic serum either with anti-IL-10 antibodies or anti-TGF-β antibodies and then stimulated with endotoxin. Measurements: TNF-α, IL-10, and TGF-β levels were measured in the serum and in culture supernatants by enzyme-linked immunosorbent assay. Setting: Research laboratory. Main Results: IL-10 and TNF-α levels were significantly increased in septic serum, whereas TGF-β levels were not different from controls. Normal monocytes increased TNF-α and IL-10 release in response to endotoxin. In contrast, septic monocyte TNF-α release was attenuated in response to endotoxin (1.8 ± 0.5 vs. 1.0 ± 0.4 ng/mL, stimulated vs. baseline), whereas IL-10 release increased significantly from baseline (173 ± 91 vs. 8 ± 4 pg/mL, stimulated vs. baseline). Incubation of normal monocytes with septic serum attenuated TNF-α release in response to endotoxin (32% ± 8% of normal serum; p <.01), whereas IL-10 release was increased (285% ± 84% of normal serum; p <.05). When normal monocytes were incubated with septic serum combined with anti-IL-10 antibodies, TNF-α release increased significantly to 75% ± 17% of normal serum (p <.05 vs. septic serum alone). Incubation of normal monocytes with anti-TGF-β antibodies did not significantly affect either TNF-α or IL-10 release in response to endotoxin. Conclusion: Monocytes from patients with septic shock exhibit persistent IL-10 release at a time when TNF-α release is down-regulated. The continued release of IL-10 may contribute to impairment of monocyte proinflammatory cytokine release and the development of immune dysfunction in septic shock.

Original languageEnglish (US)
Pages (from-to)129-133
Number of pages5
JournalCritical Care Medicine
Volume29
Issue number1
StatePublished - 2001
Externally publishedYes

Fingerprint

Septic Shock
Interleukin-10
Monocytes
Endotoxins
Tumor Necrosis Factor-alpha
Transforming Growth Factors
Serum
Antibodies
Cytokines
Anti-Idiotypic Antibodies
Enzyme-Linked Immunosorbent Assay

Keywords

  • Cytokines
  • Endotoxin
  • Endotoxin tolerance
  • Interleukin-10
  • Monocyte
  • Septic shock
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock. / Sfeir, Tacla; Saha, Dhanonjoy C.; Astiz, Mark; Rackow, Eric C.

In: Critical Care Medicine, Vol. 29, No. 1, 2001, p. 129-133.

Research output: Contribution to journalArticle

Sfeir, Tacla ; Saha, Dhanonjoy C. ; Astiz, Mark ; Rackow, Eric C. / Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock. In: Critical Care Medicine. 2001 ; Vol. 29, No. 1. pp. 129-133.
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abstract = "Objectives: The purpose of this study was to examine the pattern of tumor necrosis factor (TNF)-α and interleukin (IL)-10 release in endotoxin-stimulated septic monocytes and to determine the role of IL-10 and transforming growth factor (TGF)-β in monocyte hyporesponsiveness during septic shock. Design: Monocytes isolated from ten healthy controls and ten patients with septic shock were incubated with endotoxin and cytokine release was assessed. Next, normal monocytes were incubated with either normal or septic serum and stimulated with endotoxin. Finally, normal monocytes were incubated with septic serum either with anti-IL-10 antibodies or anti-TGF-β antibodies and then stimulated with endotoxin. Measurements: TNF-α, IL-10, and TGF-β levels were measured in the serum and in culture supernatants by enzyme-linked immunosorbent assay. Setting: Research laboratory. Main Results: IL-10 and TNF-α levels were significantly increased in septic serum, whereas TGF-β levels were not different from controls. Normal monocytes increased TNF-α and IL-10 release in response to endotoxin. In contrast, septic monocyte TNF-α release was attenuated in response to endotoxin (1.8 ± 0.5 vs. 1.0 ± 0.4 ng/mL, stimulated vs. baseline), whereas IL-10 release increased significantly from baseline (173 ± 91 vs. 8 ± 4 pg/mL, stimulated vs. baseline). Incubation of normal monocytes with septic serum attenuated TNF-α release in response to endotoxin (32{\%} ± 8{\%} of normal serum; p <.01), whereas IL-10 release was increased (285{\%} ± 84{\%} of normal serum; p <.05). When normal monocytes were incubated with septic serum combined with anti-IL-10 antibodies, TNF-α release increased significantly to 75{\%} ± 17{\%} of normal serum (p <.05 vs. septic serum alone). Incubation of normal monocytes with anti-TGF-β antibodies did not significantly affect either TNF-α or IL-10 release in response to endotoxin. Conclusion: Monocytes from patients with septic shock exhibit persistent IL-10 release at a time when TNF-α release is down-regulated. The continued release of IL-10 may contribute to impairment of monocyte proinflammatory cytokine release and the development of immune dysfunction in septic shock.",
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T1 - Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock

AU - Sfeir, Tacla

AU - Saha, Dhanonjoy C.

AU - Astiz, Mark

AU - Rackow, Eric C.

PY - 2001

Y1 - 2001

N2 - Objectives: The purpose of this study was to examine the pattern of tumor necrosis factor (TNF)-α and interleukin (IL)-10 release in endotoxin-stimulated septic monocytes and to determine the role of IL-10 and transforming growth factor (TGF)-β in monocyte hyporesponsiveness during septic shock. Design: Monocytes isolated from ten healthy controls and ten patients with septic shock were incubated with endotoxin and cytokine release was assessed. Next, normal monocytes were incubated with either normal or septic serum and stimulated with endotoxin. Finally, normal monocytes were incubated with septic serum either with anti-IL-10 antibodies or anti-TGF-β antibodies and then stimulated with endotoxin. Measurements: TNF-α, IL-10, and TGF-β levels were measured in the serum and in culture supernatants by enzyme-linked immunosorbent assay. Setting: Research laboratory. Main Results: IL-10 and TNF-α levels were significantly increased in septic serum, whereas TGF-β levels were not different from controls. Normal monocytes increased TNF-α and IL-10 release in response to endotoxin. In contrast, septic monocyte TNF-α release was attenuated in response to endotoxin (1.8 ± 0.5 vs. 1.0 ± 0.4 ng/mL, stimulated vs. baseline), whereas IL-10 release increased significantly from baseline (173 ± 91 vs. 8 ± 4 pg/mL, stimulated vs. baseline). Incubation of normal monocytes with septic serum attenuated TNF-α release in response to endotoxin (32% ± 8% of normal serum; p <.01), whereas IL-10 release was increased (285% ± 84% of normal serum; p <.05). When normal monocytes were incubated with septic serum combined with anti-IL-10 antibodies, TNF-α release increased significantly to 75% ± 17% of normal serum (p <.05 vs. septic serum alone). Incubation of normal monocytes with anti-TGF-β antibodies did not significantly affect either TNF-α or IL-10 release in response to endotoxin. Conclusion: Monocytes from patients with septic shock exhibit persistent IL-10 release at a time when TNF-α release is down-regulated. The continued release of IL-10 may contribute to impairment of monocyte proinflammatory cytokine release and the development of immune dysfunction in septic shock.

AB - Objectives: The purpose of this study was to examine the pattern of tumor necrosis factor (TNF)-α and interleukin (IL)-10 release in endotoxin-stimulated septic monocytes and to determine the role of IL-10 and transforming growth factor (TGF)-β in monocyte hyporesponsiveness during septic shock. Design: Monocytes isolated from ten healthy controls and ten patients with septic shock were incubated with endotoxin and cytokine release was assessed. Next, normal monocytes were incubated with either normal or septic serum and stimulated with endotoxin. Finally, normal monocytes were incubated with septic serum either with anti-IL-10 antibodies or anti-TGF-β antibodies and then stimulated with endotoxin. Measurements: TNF-α, IL-10, and TGF-β levels were measured in the serum and in culture supernatants by enzyme-linked immunosorbent assay. Setting: Research laboratory. Main Results: IL-10 and TNF-α levels were significantly increased in septic serum, whereas TGF-β levels were not different from controls. Normal monocytes increased TNF-α and IL-10 release in response to endotoxin. In contrast, septic monocyte TNF-α release was attenuated in response to endotoxin (1.8 ± 0.5 vs. 1.0 ± 0.4 ng/mL, stimulated vs. baseline), whereas IL-10 release increased significantly from baseline (173 ± 91 vs. 8 ± 4 pg/mL, stimulated vs. baseline). Incubation of normal monocytes with septic serum attenuated TNF-α release in response to endotoxin (32% ± 8% of normal serum; p <.01), whereas IL-10 release was increased (285% ± 84% of normal serum; p <.05). When normal monocytes were incubated with septic serum combined with anti-IL-10 antibodies, TNF-α release increased significantly to 75% ± 17% of normal serum (p <.05 vs. septic serum alone). Incubation of normal monocytes with anti-TGF-β antibodies did not significantly affect either TNF-α or IL-10 release in response to endotoxin. Conclusion: Monocytes from patients with septic shock exhibit persistent IL-10 release at a time when TNF-α release is down-regulated. The continued release of IL-10 may contribute to impairment of monocyte proinflammatory cytokine release and the development of immune dysfunction in septic shock.

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KW - Endotoxin

KW - Endotoxin tolerance

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KW - Monocyte

KW - Septic shock

KW - Transforming growth factor-β

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