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1

Staphylococcal superantigens: do they play a role in sepsis?

100%

Holtfreter S., Broker B. M.

Archivum Immunologiae et Therapiae Experimentalis

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2005

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vol. 53

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issue 1

13-27

EN

In Staphylococcus aureus, 19 different superantigens (SAgs) have been described. Their genes are all located on mobile genetic elements, such as pathogenicity islands, plasmids, and phages. SAgs bypass conventional antigen recognition by directly cross-linking major histocompatibility complex class II (MHCII) molecules on antigen-presenting cells with T cell receptors. This leads to massive T cell proliferation and cytokine release, which may end in toxic shock syndrome. The role of SAgs in other forms of sepsis is less well defined. In animal models, SAgs and lipopolysaccharide (LPS) very efficiently synergize in the induction of lethal shock, and on the basis of these observations a two-hit model of sepsis has been proposed: LPS or another monocyte stimulus hits first, then SAg or another T cell stimulus hits. In clinical studies, however, evidence for an involvement of SAgs in sepsis has been difficult to obtain. This may have a number of reasons: differences between humans and rodents in their response to LPS and SAg, heterogeneity of SAg combinations in S. aureus clinical isolates, lack of tools to analyze SAg effects in patients, blocking anti-SAg serum antibodies, and MHCII polymorphisms.

2

Peroxisome proliferator-activated receptor gamma (PPARgamma) and sepsis

100%

von_ K. A., Soller M., Brune B.

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2007

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vol. 55

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issue 1

19-25

EN

This review describes the role of the nuclear hormone receptor PPARgamma as a double-edged sword in sepsis. On the one hand, PPARgamma inhibits pro-inflammatory gene expression, predominantly by scavenging transcription factors and their cofactors, thus preventing them from binding to their cognate binding sites in the promoters of target genes. The expressions of the affected genes, such as those for inducible nitric oxide synthase, TNF-alpha, or IL-1beta are repressed. Therefore, PPARgamma is suggested to be beneficial in hyper-inflammatory diseases, such as sepsis. In n animal models of sepsis, PPARgamma agonist pretreatment auspiciously attenuated inflammation compared with control animals, accompanied by their improved survival rate. On the other hand, PPARgamma provokes apoptosis, which in the hyper-inflammatory phase of sepsis might be helpful because the number of immune cells, such as monocytes, macrophages, and neutrophils, involved in secreting high amounts of pro-inflammatory mediators will be reduced. In contrast, during the anti-inflammatory phase, cell death of immune cells, especially of T lymphocytes, is supposed to be deleterious. Under these circumstances, a second infection cannot be adequately answered, thus causing septic shock and multi-organ dysfunction syndrome. Therefore the role of PPARgamma is still ambiguous. Particularly its role in initiating apoptosis awaits further clarification to finally elucidate its impact on sepsis development.

3

Proinflammatory cytokines (IL-6, IL-8), cytokine inhibitors (IL-6 sR, sTNFR II) and anti-inflammatory cytokines (IL-10, IL-13) in the pathogenesis of sepsis in newborns and infants

100%

Sikora J. P., Chlebna-Sokol D., Krzyzanska-Oberbek A.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 5

399-405

EN

The levels of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8, and the anti-inflammatory cytokines IL-10 and IL-13 were studied in child patients with sepsis. The changes of the cytokines inhibitors soluble IL-6 receptor and soluble p75 TNF alpha receptor were also investigated in the patients' sera. An increase of pro- and anti-inflammatory cytokine levels was demonstrated at the time of diagnosis. Pharmacotherpy was accompanied by a decrease of the elevated concentrations of both cytokines and their inhibitors. The time pattern of changes in cytokine and cytokine inhibitor serum concentrations along with the time course of acute phase indices, including procalcitonin and C-reactive protein, allows for an evaluation of system inflammatory response and may support diagnostic and prognosis methods.

4

Proinflammatory cytokine inhibitors, TNF- and oxidative burst of polymorphonuclear leukocytes in the pathogenesis of sepsis in newborns

100%

Sikora J. P., Chlebna-Sokol D., Dabrowska I., Lipczynski D., Chrul S.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 2

155-162

EN

This study was to evaluate the levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF-) and the cytokine inhibitors soluble TNF- receptor (sTNFR) and IL-1 receptor antagonist (IL-1 ra) as well as the intensity of oxidative metabolism of peripheral blood polymorphonuclear leukocytes in the course of sepsis in newborns. An increase of TNF-, sTNFR and IL-1 ra concentrations was found in the blood serum of the patients at the time of diagnosis. This was further accompanied by polymorphonuclear leukocyte stimulation and, as a consequence of prolonged bacterial antigen stimulation, functional exhaustion of these cells and their diminished oxidative metabolism was observed. Within the same time period, an enhanced expression of p55 and p75 TNF- receptors on polymorphonuclear leukocyte cell surfaces was found. It was indicated that the applied pharmacotherapy caused a decrease of the initially elevated concentrations of TNF- and proinflammatory cytokine inhibitors (sTNFR, IL-1 ra). The intensive therapy of sepsis was associated with the increased oxidative burst of polymorphonuclear leukocytes along with the decrease of p55 and p75 expression on their cell surfaces.

5

Immunotherapy in the management of sepsis

88%

Sikora J. P.

Archivum Immunologiae et Therapiae Experimentalis

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2002

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vol. 50

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issue 5

317-324

EN

The work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so called ?respiratory burst? of neutrophils and antioxidant mechanisms of the host are also discussed. The work has focused on possible approaches to the management of sepsis connected with immunotherapy. Neutralisation of endotoxin lypopolysaccharide (LPS), anti-TNF-alpha therapy with monoclonal antibodies or pentoxifylline (PTXF) as well as soluble recombinant cytokine agonists and antagonists used in clinical trials were taken into consideration. Besides, cytokine manipulation therapy, anti-adhesion techniques or glicocorticoides and antioxidant barrier interference were also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts aggressive examination of the immune system, aimed at affecting its function.

6

Biological activities of lipopolysaccharide

88%

Lukasiewicz J., Lugowski C.

Postępy Higieny i Medycyny Doświadczalnej

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2003

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vol. 57

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issue 1

33-53

EN

Lipopolysaccharides (LPS, endotoxin) are known to be responsible for the initiation of endotoxic shock, therefore they can be targets for new preventive and therapeutic strategies. This review describes the biological and physicochemical properties of endotoxin ? major component of the outer membrane of Gram-negative bacteria. The paper focuses on response of the host to endotoxin, recent knowledge about the target cells and receptors for LPS, mechanisms of innate immune response and cell signal transduction due to the LPS recognition. It also summaries results of studies on LPS structure influence on its biological activity.

7

Stroke, myocardial infarction, acute and chronic inflammatory diseases: caspases and other apoptotic molecules as targets for drug development

88%

Kreuter M., Langer C., Kerkhoff C., Reddanna P., Kania A. L., Maddika S., Chlichlia C., Bui T. N., Los M.

Archivum Immunologiae et Therapiae Experimentalis

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2004

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vol. 52

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issue 3

141-155

EN

Mapping of the human and other eukaryotic genomes has provided the pharmacological industry with excellent models for drug discovery. Control of cell proliferation, differentiation, activation and cell removal is crucial for the development and existence of multicellular organisms. Each cell cycle progression, with sequences of DNA replication, mitosis, and cell division, is a tightly controlled and complicated process that, when deregulated, may become dangerous not only to a single cell, but also to the whole organism. Regulation and the proper control of the cell cycle and of programmed cell death (apoptosis) is therefore essential for mammalian development and the homeostasis of the immune system. The molecular networks that regulate these processes are critical targets for drug development, gene therapy, and metabolic engineering. In addition to the primary, intracellular apoptotic suicide machinery, components of the immune system can detect and remove cells and tissue fragments that no longer serve their defined functions. In this review we will focus on apoptotic pathways converging on caspase family proteases, summarizing pharmacological attempts that target genes, proteins, and intermolecular interactions capable of modulating apoptosis and the inflammatory response. The upcoming pharmacological development for treatment of acute pathologies, such as sepsis, SIRS, stroke, traumatic brain injury, myocardial infarction, spinal cord injury, acute liver failure, as well as chronic disorders such as Huntington's disease, Parkinson's disease, ALS, and rheumatoid arthritis, will be discussed in details. We also suggest new potential molecular targets that may prove to be effective in controlling apoptosis and the immune response in vivo.

8

Prognostic markers of sepsis and septic shock

88%

Kubler-Kielb J., Adamik B.

Postępy Higieny i Medycyny Doświadczalnej

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2000

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vol. 54

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issue 2

119-132

EN

The first stage of systemic inflammatory response during sepsis and septic shock is the massive production of proinflammatory cytokines. Numerous clinical trials were done investigating various agents that were thought to stop this reaction. The results, however, were disappointing. Then it was realised that massive production of antiinflammatory cytokines could also be delirious. Persistent immunosupression in the course of sepsis increaased the risk of death. Therefore the proper balance between pro- and antiinflammatory mediators is extremely important and the methodologies available for monitoring immunological status in patients with sepsis and septic shock are currently of great interest.

9

The therapeutic potential of interleukin 10 in infection and inflammation

88%

Kumar A., Creery W. D.

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vol. 48

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issue 5

529-537

EN

Interleukin 10 (IL-10), a cytokine with inhibitory activity on inflammation and cell -mediated immune responses (CMIR), holds enormous potential for the treatment of inflammatory and autoimmune disorders. In addition, IL-10 has also been implicated in the immunopathogenesis of a number of infectious diseases through the use of IL-10 knock-out or IL-10 transgenic mouse models. In this review, we delineate infectious and inflammatory conditions in which IL-10 has shown potential for therapeutic manipulation. Specifically, we review the role of IL-10 in human endotoxemia/sepsis and in HIV infection, conditions for which preliminary phase I trials have recently been undertaken. It is suggested that the therapeutic potential of IL-10 to selectively ameliorate human infectious and inflammatory processes can be realized through a careful selection of the clinical conditions in which patients are undergoing concomitant treatment with anti-microbial regimens.

Refine search results

Staphylococcal superantigens: do they play a role in sepsis?

Peroxisome proliferator-activated receptor gamma (PPARgamma) and sepsis

Proinflammatory cytokines (IL-6, IL-8), cytokine inhibitors (IL-6 sR, sTNFR II) and anti-inflammatory cytokines (IL-10, IL-13) in the pathogenesis of sepsis in newborns and infants

Proinflammatory cytokine inhibitors, TNF- and oxidative burst of polymorphonuclear leukocytes in the pathogenesis of sepsis in newborns

Immunotherapy in the management of sepsis

Biological activities of lipopolysaccharide

Stroke, myocardial infarction, acute and chronic inflammatory diseases: caspases and other apoptotic molecules as targets for drug development

Prognostic markers of sepsis and septic shock

The therapeutic potential of interleukin 10 in infection and inflammation