Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide-stimulated whole blood cells: Roles of interleukin-10 and the extracorporeal circuit

Dehoux, Monique; Hernot, Sylvie; Asehnoune, Karim; Boutten, Anne; Paquin, S.; Leçon-Malas, Véronique; Toueg, Marie-Laure; Desmonts, Jean-Marie; Durand, Geneviève; Philip, Ivan

doi:10.1097/00003246-200006000-00004

Cited by 35 publications

(29 citation statements)

References 37 publications

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“…The anti-inflammatory phase in systemic inflammation is associated with a reduced TLR responsiveness of monocytes [14], [15]. Monocytes respond to LPS stimulation through the association of LPS/LPS-binding protein (LBP) with CD14 and TLR4 [16], [17], which results in NF-κB activation.…”

Section: Introductionmentioning

confidence: 99%

STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass

et al. 2012

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BackgroundCardiopulmonary bypass (CPB) surgery initiates a controlled systemic inflammatory response characterized by a cytokine storm, monocytosis and transient monocyte activation. However, the responsiveness of monocytes to Toll-like receptor (TLR)-mediated activation decreases throughout the postoperative course. The purpose of this study was to identify the major signaling pathway involved in plasma-mediated inhibition of LPS-induced tumor necrosis factor (TNF)-α production by monocytes.Methodology/Principal FindingsPediatric patients that underwent CPB-assisted surgical correction of simple congenital heart defects were enrolled (n = 38). Peripheral blood mononuclear cells (PBMC) and plasma samples were isolated at consecutive time points. Patient plasma samples were added back to monocytes obtained pre-operatively for ex vivo LPS stimulations and TNF-α and IL-6 production was measured by flow cytometry. LPS-induced p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation by patient plasma was assessed by Western blotting. A cell-permeable peptide inhibitor was used to block STAT3 signaling. We found that plasma samples obtained 4 h after surgery, regardless of pre-operative dexamethasone treatment, potently inhibited LPS-induced TNF-α but not IL-6 synthesis by monocytes. This was not associated with attenuation of p38 MAPK activation or IκB-α degradation. However, abrogation of the IL-10/STAT3 pathway restored LPS-induced TNF-α production in the presence of suppressive patient plasma.Conclusions/SignificanceOur findings suggest that STAT3 signaling plays a crucial role in the downregulation of TNF-α synthesis by human monocytes in the course of systemic inflammation in vivo. Thus, STAT3 might be a potential molecular target for pharmacological intervention in clinical syndromes characterized by systemic inflammation.

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Section: Introductionmentioning

confidence: 99%

STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass

et al. 2012

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“…The reactivity of polymorphonuclear neutrophils is also depressed by anti-inflammatory cytokines after surgery with cardiopulmonary bypass [11]. Recently, Dehoux et al [12] demonstrated that blood cells from patients undergoing cardiopulmonary bypass rapidly become hyporesponsive to endotoxin and that interleukin (IL)-10 is partly involved in this process. These findings suggest that blood cells have a self-limiting capacity in response to the severity of systemic inflammation after surgery.…”

Section: Introductionmentioning

confidence: 99%

An increase in urinary nitrite/nitrate excretion is associated with the hyperdynamic state after cardiovascular surgery

et al. 2002

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“…Elevated levels of proinflammatory cytokines, such as tumor necrosis factor-a, interleukin (IL)-6, and IL-8, have been reported [6,11]. This inflammatory response is counterbalanced by a complex system of inhibitors, such as IL-10 and soluble cytokine receptors [7,10,25].…”

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confidence: 99%

Administration of Steroids in Pediatric Cardiac Surgery: Impact on Clinical Outcome and Systemic Inflammatory Response

Gessler¹,

Hohl²,

Carrel

et al. 2005

Pediatr Cardiol

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Abstract. Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response. Pre-bypass steroid administration may modulate the inflammatory response, resulting in improved postoperative recovery. We performed a prospective study in the departments of cardiovascular surgery and pediatric intensive care medicine of two university hospitals that included 50 infants who underwent heart surgery. Patients received either prednisolone (30 mg/ kg) added to the priming solution of the cardiopulmonary bypass circuit (steroid group) or no steroids (nonsteroid group). Clinical outcome parameters include therapy with inotropic drugs, oxygenation, blood lactate, glucose, and creatinine, and laboratory parameters of inflammation include leukocytes, C-reactive protein, and interleukin-8. Postoperative recovery (e.g., the number, dosage, and duration of inotropic drugs as well as oxygenation) was similar in patients treated with or without steroids when corrected for the type of cardiac surgery performed. After CPB, there was an inflammatory reaction, especially in patients with a long CPB time. Postoperative plasma levels of interleukin-8 were correlated with the duration of CPB time (r = 0.62, p < 0.001). Administration of steroids had no significant impact on the laboratory parameters of inflammation. Administration of prednisolone into the priming solution of the CPB circuit had no measurable influence on postoperative recovery and did not suppress the inflammatory response.

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Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide-stimulated whole blood cells: Roles of interleukin-10 and the extracorporeal circuit

Cited by 35 publications

References 37 publications

STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass

STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass

An increase in urinary nitrite/nitrate excretion is associated with the hyperdynamic state after cardiovascular surgery

Administration of Steroids in Pediatric Cardiac Surgery: Impact on Clinical Outcome and Systemic Inflammatory Response

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