Proinflammatory Cytokine Gene Expression in Whole Blood From Patients Undergoing Coronary Artery Bypass Surgery and Its Modulation by Pentoxifylline

Kleinschmidt, S.; Wanner, Guido A.; Bussmann, D.; Kremer, Jean-Pierre; Ziegenfuß, Thomas; Menger, Michael D.; Bauer, Michael

doi:10.1097/00024382-199801000-00002

Cited by 31 publications

(34 citation statements)

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“…TNF-a synthesis did not recover by the 6 th postoperative day. These data concur with previous observations in cardiac surgical patients [8,9]. Similar endotoxin hyporesponsiveness has been described in patients undergoing abdominal aortic aneurysm repair [12], in polytraumatized [13] and septic patients [14], in whom it was related to clinical outcome.…”

Section: Discussionsupporting

confidence: 92%

“…This results in immune system deterioration and eventually to increased susceptibility to infections [7]. Specific functions of polymorphonuclear neutrophils (PMN), i. e. cytokine production or proliferation [8,9] and HLA-DR expression on monocytes [10,11] are diminished after CPB. Downregulation of TNF-a-synthesis after CPB is at least in part induced by circulating cytokine-inhibitory activities.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators in vivo and in vitro

et al. 2007

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators in vivo and in vitro

et al. 2007

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“…Severe trauma induces a systemic inflammatory response that can eventually lead to remote organ dysfunction and secondary organ failure (9,10). The innate immune system is the first line of posttraumatic immune response, initiating further cellular activation.…”

Section: Pf4 Induces Natural Killer Cells To Release Interleukin-8 (3)mentioning

confidence: 99%

Platelet Factor 4 Is Highly Upregulated in Dendritic Cells after Severe Trauma

Maier

Geiger

Henrich

et al. 2009

Mol Med

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Dendritic cells (DCs) represent an important linkage between the innate and adaptive immune system and express proinflammatory transcriptomic products early after trauma. The use of a genomic approach recently revealed that platelet factor 4 (PF4) is significantly upregulated in DCs in patients after multiple trauma. However, knowledge about subsequent PF4 alteration and its potential clinical relevance in the context of multiple trauma is still limited. We used quantitative reverse transcription-polymerase chain reaction to analyze PF4 expression in both myeloid DCs (MDCs) and plasmocytoid DCs (PDCs) isolated from 10 patients after multiple trauma. Intracellular PF4 as well as HLA-DR expression were detected by flow cytometry. Furthermore, DCs and peripheral blood mononuclear cells were incubated on a monolayer of human umbilical endothelial cells and their adhesion properties were analyzed. The ratio of the DC subtypes (MDC and PDC) was assessed by flow cytometry. PF4 expression significantly increased on d 1 and d 2 as measured by reverse transcription-polymerase chain reaction. Intracellular PF4 content in MDCs and PDCs was significantly elevated in trauma patients compared with healthy controls. In addition, the surface antigen HLA-DR on MDCs was significantly elevated on d 1 and d 4 after trauma in patients compared with controls. However, cell adhesion of DCs did not show any significant differences between patients and controls. PF4 concentration in MDCs and PDCs significantly correlated with the injury severity score. These results confirm an early and subsequent posttraumatic activation of PF4 in DCs. PF4 also participates in the posttraumatic activation of DCs in relation to injury severity, a role that might be preferably based on the modification of receptor expression, whereas adhesion properties are largely unaffected.

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“…LPS injection. Early transient LPS tolerance differs in its kinetics from classical LPS (or endotoxin) tolerance, observed in experimental animals (6) and leukocytes of patients with sepsis (7)(8)(9)(10), systemic inflammatory response syndrome (11), major surgery (12), and trauma (13,14), which lasts for several days to weeks. The induction of LPS tolerance during these clinical conditions may in the short term be beneficial by preventing excessive inflammation, but in the longer term be deleterious by hampering an adequate defense response to opportunistic infections.…”

mentioning

confidence: 94%

In Vivo Lipopolysaccharide Exposure of Human Blood Leukocytes Induces Cross-Tolerance to Multiple TLR Ligands

Vos

Pater

Pangaart

et al. 2009

The Journal of Immunology

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In vitro and in vivo experiments in mice have shown that exposure of cells to the TLR4 ligand LPS induces tolerance toward a second exposure to LPS and induces cross-tolerance to certain other TLR ligands. Recently, we found that LPS tolerance in experimental human endotoxemia and Gram-negative sepsis is associated with elevated levels of IL-1R-associated kinase M, an intracellular negative regulator of MyD88-dependent TLR signaling. In the present study, we investigated whether in vivo exposure of humans to LPS induces tolerance in circulating leukocytes to other TLR agonists that rely either on MyD88- dependent or on MyD88-independent signaling. Analysis of TNF, IL-1β, IL-6, and IL-10 levels in whole blood demonstrated that leukocytes were hyporesponsive to ex vivo LPS restimulation 3–8 h after i.v. LPS injection (4 ng/kg). Reduced cytokine release during the same interval was also observed in whole blood further stimulated with MyD88-dependent ligands for TLR2, TLR5, and TLR7 or with whole bacteria. Strikingly, blood leukocytes were also tolerant to a ligand for TLR3, which signals solely through a MyD88-independent (Toll IL-1R domain-containing adaptor-inducing IFN-β (TRIF)-dependent) pathway. The hyporesponsiveness of leukocytes to TLR3 ligation was associated with reduced rather than increased levels of the recently identified TRIF inhibitor SARM. Taken together, these data indicate that systemic LPS challenge of human volunteers induces cross-tolerance to multiple TLR ligands that signal in a MyD88-dependent or MyD88-independent manner and suggest that LPS exposure of human blood leukocytes may hamper the inflammatory response to various microbial components.

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Proinflammatory Cytokine Gene Expression in Whole Blood From Patients Undergoing Coronary Artery Bypass Surgery and Its Modulation by Pentoxifylline

Cited by 31 publications

References 0 publications

Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators in vivo and in vitro

Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators in vivo and in vitro

Platelet Factor 4 Is Highly Upregulated in Dendritic Cells after Severe Trauma

In Vivo Lipopolysaccharide Exposure of Human Blood Leukocytes Induces Cross-Tolerance to Multiple TLR Ligands

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