Interleukin 6—A Potential Mediator of Lethal Sepsis After Major Thermal Trauma: Evidence for Increased IL-6 Production by Peripheral Blood Mononuclear Cells

Schlüter, B.; König, Brigitte; Bergmann, Uwe; Müller, F. E.; König, Wolfgang

doi:10.1097/00005373-199112000-00017

Cited by 105 publications

(39 citation statements)

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“…A multicenter study showed that IL-6 can predict survival on the 28 th day after sepsis onset [40] . The value of IL-6 to distinguish between SIRS and sepsis is controversially discussed [41,42] , since high levels can also be detected after trauma, surgery or in patients with autoimmune diseases [43][44][45] . Nevertheless, the IL-6 expression correlates with sepsis severity [10] .…”

Section: Il-6mentioning

confidence: 99%

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

Kojic

Siegler

Uhle

et al. 2015

WJEM

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Beside many efforts to improve outcome, sepsis is still one of the most frequent causes of death in critically ill patients. It is the most common condition with high mortality in intensive care units. The complexity of the septic syndrome comprises immunological aspects -i.e. , sepsis induced immunosuppression -but is not restricted to this fact in modern concepts. So far, exact mechanisms and variables determining outcome and mortality stay unclear. Since there is no typical risk profile, early diagnosis and risk stratification remain difficult, which hinders rapid and effective treatment initiation. Due to the heterogeneous nature of sepsis, potential therapy options should be adapted to the individual. Biomarkers like C-reactive protein and procalcitonin are routinely used as complementary tools in clinical decision-making. Beyond the acute phase proteins, a wide bunch of promising substances and non-laboratory tools with potential diagnostic and prognostic value is under intensive investigation. So far, clinical decision just based on biomarker assessment is not yet feasible. However, biomarkers should be considered as a complementary approach. Core tip: Sepsis is a complex continuum of disturbed systems. Despite the presence of clinical consensus criteria, the early diagnosis especially in the perioperative setting is challenging. A magnitude of potential new biomarkers is tested for this purpose, but evidence is mounting that due to the complex nature of the syndrome, biomarkers are rather complementary tools for clinical decision making than "magic bullets". Moreover, biomarkers are also evaluated for therapy guidance, linking diagnostic results to an individual therapeutic regime. This review summarizes the developments in the biomarker field, aiming to provide an overview about current targets and their limitations.

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Section: Il-6mentioning

confidence: 99%

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

Kojic

Siegler

Uhle

et al. 2015

WJEM

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“…Among these cytokines, IL-6 seems to play a central role in the development of the systemic inflammatory reaction, finally leading to septic shock (5 ). IL-6 is a pleiotropic cytokine secreted mainly by monocytes and macrophages.…”

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confidence: 99%

“…Several studies have indicated that plasma concentrations of IL-6 are closely related with the severity and outcome of sepsis, suggesting a pathogenetic role of IL-6 (2,5 ). IL-6 has a short half-life in vivo (Ͻ10 min) (7 ); therefore, plasma concentrations of IL-6 are regulated mainly at the level of RNA expression.…”

mentioning

confidence: 99%

The Interleukin-6 G(−174)C Promoter Polymorphism Does Not Determine Plasma Interleukin-6 Concentrations in Experimental Endotoxemia in Humans

Endler¹,

Marsik²,

Joukhadar³

et al. 2004

Clinical Chemistry

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Background: Interleukin 6 (IL-6) is a pleiotropic cytokine that plays an essential role in the pathogenesis of acute and chronic infections. As the role of the IL-6 G(؊174)C polymorphism in determining serum concentrations of IL-6 is controversial, we studied the genotype-specific IL-6 response in a well-standardized model of systemic inflammation. Methods: A total of 76 healthy young males (age range, 19 -35 years) received a single bolus of 2 ng/kg endotoxin [lipopolysaccharide (LPS)] intravenously. Plasma IL-6 was measured by enzyme immunoassay at 0, 2, 6, and 24 h after LPS infusion, and the IL-6 promoter genotype was analyzed by a mutagenic separated PCR assay. Results: IL-6 increased 300-fold 2 h after LPS challenge and returned almost to normal within 24 h. Neither basal IL-6 nor the IL-6 response to LPS was significantly affected by the IL-6 promoter genotype. Conclusions: The IL-6 G(؊174)C promoter polymorphism does not significantly influence basal concentrations of IL-6 or peak IL-6 in human endotoxemia.

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“…Along with TNF-and IL-1, it is believed to be a key mediator in the response to stress and pathophysiology of multi-organ failure. High serum levels of IL-6 have been correlated with severe sepsis and worse outcome from sepsis [129][130][131][132][133][134][135][136][137].…”

Section: Interleukin 6 (Il-6)mentioning

confidence: 99%

“…The association with lower mortality is independent of age and APACHE II score at admission [265]. The association with reduced mortality may be related to the increased fibrinogen A2 allele associated with variable levels of IL-1RA; A2 associated with increased risk of in adults but not children with sepsis; A2 associated with increased mortality in adults with sepsis; +2018 "2 allele" associated with increased mortality in children with meningococcal disease and more severe lung disease in children with pneumonia [120,122,[125][126][127][128] IL-6 -174 G/C G associated with increased IL-6 levels in adult patients but decreased levels in neonates; C associated with increased levels in monocytes from neonates, sepsis in neonates, and severe sepsis and organ dysfunction in children [130,[142][143][144][145][146]281] levels among patients with the GAA haplotype since the 455 A allele within the haplotype is associated with increased transcription. Another polymorphism in the fibrinogen gene, the Val34Leu polymorphism is known to alter the fibrin meshwork with variable permeation characteristics.…”

Section: Fibrinogenmentioning

confidence: 99%

Host Genetics and Pediatric Sepsis

Quasney¹

2011

TOINFJ

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Susceptibility to, and outcome from, sepsis in children is highly variable due in part to genetic variation in genes coding for components of the innate immune response. This review article will discuss evidence for the influence of host genetic variability on the susceptibility to, and outcome from, sepsis in children and adults. Polymorphisms in genes coding for proteins involved in the recognition of bacterial pathogens (TLR4, CD-14, Fc RIIa, and mannose binding lectin) and the response to bacterial pathogens (TNF-, IL-1 , IL-1 , IL-1 RA , IL-6, IL-10, heat shock proteins, ACE, plasminogen activator inhibitor-1) can influence the amount or function of the protein produced in response to bacterial stimuli. Evidence is discussed suggesting that some of these genetic polymorphisms influence the susceptibility to, and outcome from, sepsis. Conclusion:Host genetic variability in the regulatory and coding regions of genes for components of the innate immune system may influence the susceptibility to and/or outcome from sepsis. The disparate results observed in many studies of polymorphisms in sepsis emphasize the need for future studies to be larger, to include the analysis of multiple polymorphisms, and to be better designed with respect to control populations in order to identify the degree of influence that genetic variability has on sepsis.

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Interleukin 6—A Potential Mediator of Lethal Sepsis After Major Thermal Trauma: Evidence for Increased IL-6 Production by Peripheral Blood Mononuclear Cells

Cited by 105 publications

References 0 publications

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

The Interleukin-6 G(−174)C Promoter Polymorphism Does Not Determine Plasma Interleukin-6 Concentrations in Experimental Endotoxemia in Humans

Host Genetics and Pediatric Sepsis

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