scholarly journals Επίδραση συνεχούς φλεβοφλεβικής αιμοδιήθησης στην αιμοδυναμική και αναπνευστική λειτουργία, στην πρόγνωση καθώς και στην κινητική κυτταροκινών βαρειά σηπτικών ασθενών της ΜΕΘ

2011 ◽  
Author(s):  
Κωνσταντίνος Περρέας
Keyword(s):  
Severe Sepsis ◽  
Renal Dysfunction ◽  
Respiratory Function ◽  
Cytokine Production ◽  
Therapeutic Benefits ◽  
Septic Episode ◽  
Tnf Α ◽  
Multiple Blood ◽  
High Concentrations ◽  
Kinetics Of

Introduction Renal dysfunction and failure is a common consequence of the frequently encountered sepsis affecting critically ill patients. This is managed amongst others with the use of continuous renal replacement methods. This study was intended to explore the effects of CCRT beyond the established therapeutic benefits on the patients’ haemodynamics, organ dysfunction and cytokine kinetics of the SIRS that chracterise this multifacet syndrome. Questions that we set to answer in detail: Does CVVH influence cytokine kinetics for cytokines TNF-α, IL-6 and IL-1β ? How does it affect patient haemodynamics? How does it affect prognosis? We conducted 3 studies: A. Pilot study We measured clearance and concentrations of the cytokines under investigation in multiple blood and ultrafiltrate specimens and varying CVVH settings in 9 septic patients receiving renal replacement for acute renal failure. Results: We confirmed constantly high concentrations as well as brief bursts of cytokine production. The preferred circuit and flow for maximal clearance was set. B. Study no. 2 Hypothesis : Does CVVH improve haemodynamic and respiratory function? Method: 36 patients with severe sepsis were monitored for indices of haemodynamic and respiratory function while on CVVH. The filter was discontinued for 12 hrs for control within the cohort. Results: MAP, SVR and vasopressor requirements improved during CVVH with transient worsening during discontinuation. These differences were more pronounced in the group of patients that survived. C. Study no. 3 Hypothesis: Is the effected imroved haemodynamic status linked with imroved survival when applied as early as possible in patients with renal dysfunction? How does this affect cytokine kinetics? Methods: 30 consecutive patients with severe sepsis and/or septic shock were included in the study. CVVH was instituted as early as possible upon establishment of renal dysfunction. Clinical and laboratory indices of MOF were measured daily and plasma and ultrafiltrate specimens were taken and the investigated cytokines measured. Results: Of the measured indices MAP, SVR, CI as well as Pa02/Fi02 all improved during the course of the study, while in some of them there were also baseline differences (pre-CVVH) between survivors and non-survivors. Cytokine clearance and absorption on the membrane were quantified. Sieving coefficients were calculated for TNF- α and IL-6. A multivariate analysis of statistically significant differences between survivors and non-survivors revealed earlier institution of CVVH in the duration of the septic episode as the strongest predictor of survival.

Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice

2007 ◽  
Vol 293 (1) ◽  
pp. F325-F332 ◽  
Author(s):  
Ganesan Ramesh ◽  
Binzhi Zhang ◽  
Satoshi Uematsu ◽  
Shizuo Akira ◽  
W. Brian Reeves
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renal Dysfunction ◽  
Blood Urea Nitrogen ◽  
Cytokine Production ◽  
Moderate Increase ◽  
Urea Nitrogen ◽  
Increased Risk ◽  
Tnf Α ◽  
Synergistic Increase

A major toxicity of the cancer chemotherapeutic agent cisplatin is acute renal failure. Sepsis is a common cause of acute renal failure in humans and patients who receive cisplatin are at increased risk for sepsis. Accordingly, this study examined the interactions between cisplatin and endotoxin in vivo with respect to renal function and cytokine production. Mice were treated with either a single dose of cisplatin or two doses of LPS administered 24 h apart, or both agents in combination. Administration of 10 mg/kg cisplatin had no effect on blood urea nitrogen or creatinine levels throughout the course of the study. LPS resulted in a modest rise in blood urea nitrogen at 24 and 48 h, which returned to normal by 72 h. In contrast, mice treated with both cisplatin and LPS developed severe renal failure and an increase in mortality. Urine, but not serum, TNF-α levels showed a synergistic increase by cisplatin and LPS. Urinary IL-6, MCP-1, KC, and GM-CSF also showed a synergistic increase with cisplatin+LPS treatment. The renal dysfunction induced by cisplatin+LPS was completely dependent on TLR4 signaling and partially dependent on TNF-α production. Increased cytokine production was associated with a moderate increase in infiltrating leukocytes which was not different between cisplatin+LPS and LPS alone. These results indicate that cisplatin and LPS act synergistically to produce nephrotoxicity which may involve proinflammatory cytokine production.

scholarly journals Interleukin-10 Modulates Proinflammatory Cytokines in the Human Monocytic Cell Line THP-1 Stimulated withBorrelia burgdorferi Lipoproteins

2000 ◽  
Vol 68 (12) ◽  
pp. 6663-6669 ◽  
Author(s):  
P. K. Murthy ◽  
Vida A. Dennis ◽  
Barbara L. Lasater ◽  
Mario T. Philipp
Keyword(s):  
Cell Line ◽  
Inflammatory Cytokines ◽  
Cytokine Production ◽  
Interleukin 10 ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Human Monocytic Cell Line ◽  
Tnf Α ◽  
Human Monocytic Cell ◽  
Kinetics Of

ABSTRACT We determined previously that lipoproteins of Borrelia burgdorferi stimulate inflammatory and anti-inflammatory cytokines (interleukin-10 [IL-10]) in monocytes. IL-10 could have an effect on innate and acquired immune responses to B. burgdorferi and influence the magnitude of the infectious inoculum and disease outcome. To understand the mechanism(s) of IL-10 action during early infection, when innate immunity expressed chiefly by skin macrophages is key, we investigated the effect of exogenous and endogenous IL-10 on the production of the macrophage-derived cytokines IL-6, IL-1β, IL-12, and tumor necrosis factor alpha (TNF-α). We used the THP-1 human monocytic cell line and recombinant lipidated OspA (L-OspA) as the model target cell and stimulant, respectively. To determine the kinetics of cytokine production by THP-1 cells, we stimulated them with L-OspA and also with heat-killed B. burgdorferi cells (HBb) and lipopolysaccharide (LPS). Exogenous IL-10 dampened production of inflammatory cytokines, as elicited by lipoproteins. The inhibition of endogenous IL-10 function by anti-IL-10 antibody reduced the production of IL-12 and IL-6 but not that of IL-1β and TNF-α. An inspection of the kinetics of cytokine production clarified this finding. TNF-α was produced prior to, and IL-β was produced at the same time as, IL-10, whereas IL-6 and IL-12 were produced later. HBb, LPS, and L-OspA yielded similar kinetics of cytokine production. This result reinforces the notion that lipoproteins are the functional molecules in HBb and perhaps in vivo. It indicates also that signaling pathways utilized by LPS and lipoproteins may be extensively shared. The results are consistent with a major role played by IL-10 in controlling the initial phase of infection with this spirochete.

scholarly journals Desensitization Contributes to the Synaptic Response of Gain-of-Function Mutants of the Muscle Nicotinic Receptor

2006 ◽  
Vol 128 (5) ◽  
pp. 615-627 ◽  
Author(s):  
Sergio Elenes ◽  
Ying Ni ◽  
Gisela D. Cymes ◽  
Claudio Grosman
Keyword(s):  
Nicotinic Receptor ◽  
Dissociation Rate ◽  
Gain Of Function ◽  
Naturally Occurring ◽  
Channel Opening ◽  
Speed Up ◽  
High Concentrations ◽  
Dissociation Rate Constants ◽  
Kinetics Of ◽  
Peak Value

Although the muscle nicotinic receptor (AChR) desensitizes almost completely in the steady presence of high concentrations of acetylcholine (ACh), it is well established that AChRs do not accumulate in desensitized states under normal physiological conditions of neurotransmitter release and clearance. Quantitative considerations in the framework of plausible kinetic schemes, however, lead us to predict that mutations that speed up channel opening, slow down channel closure, and/or slow down the dissociation of neurotransmitter (i.e., gain-of-function mutations) increase the extent to which AChRs desensitize upon ACh removal. In this paper, we confirm this prediction by applying high-frequency trains of brief (∼1 ms) ACh pulses to outside-out membrane patches expressing either lab-engineered or naturally occurring (disease-causing) gain-of-function mutants. Entry into desensitization was evident in our experiments as a frequency-dependent depression in the peak value of succesive macroscopic current responses, in a manner that is remarkably consistent with the theoretical expectation. We conclude that the comparatively small depression of the macroscopic currents observed upon repetitive stimulation of the wild-type AChR is due, not to desensitization being exceedingly slow but, rather, to the particular balance between gating, entry into desensitization, and ACh dissociation rate constants. Disruption of this fine balance by, for example, mutations can lead to enhanced desensitization even if the kinetics of entry into, and recovery from, desensitization themselves are not affected. It follows that accounting for the (usually overlooked) desensitization phenomenon is essential for the correct interpretation of mutagenesis-driven structure–function relationships and for the understanding of pathological synaptic transmission at the vertebrate neuromuscular junction.

Bacteriophages immunomodulate the response of monocytes

2021 ◽  
pp. 153537022199515
Author(s):  
Lídia Perea ◽  
Lorena Rodríguez-Rubio ◽  
Juan C Nieto ◽  
Carlos Zamora ◽  
Elisabet Cantó ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Statistical Significance ◽  
Control Sample ◽  
Polymyxin B ◽  
Dependent Manner ◽  
Direct Role ◽  
Gram Positive Bacteria ◽  
Hla Dr ◽  
Tnf Α

Bacteriophages are present in fluids from cirrhosis patients. However, their effect on the immune response is unknown. In this work, we explore the role of phages in the phenotype, function, and cytokine production of monocytes. We stimulated healthy monocytes with five different butanol-purified phage suspensions infective for Gram-negative and Gram-positive bacteria. We studied the expression of the monocyte markers involved in lipopolysaccharide recognition (LPS; CD14), antigen presentation (HLA-DR) and co-stimulation (CD86), and the concentration of induced cytokines (TNF-α, IFN-α, and IL-10) by phages. To confirm the direct role of phages without the interference of contaminating soluble LPS in phage suspensions, polymyxin B was added to the cell cultures. Phagocytosis experiments were assessed by flow cytometry using labeled phage suspensions. We observed that butanol-purified phages reduced the surface levels of CD14 and CD86 in monocytes and increased the secreted levels of TNF-α and IL-10 compared with the control sample containing only butanol buffer. All phage suspensions showed downregulation of HLA-DR expression but only Staphylococcus aureus phage contaminated with Escherichia coli reached statistical significance. The addition of polymyxin B did not restore the monocytic response induced by phages, suggesting that the effect was not caused by the presence of LPS. Monocytes were able to phagocyte phages in a dose- and time-dependent manner. To conclude, the phagocytosis of butanol-purified phages altered the phenotype and cytokine production of monocytes suggesting they become tolerogenic.

Serum lipid profile, cytokine production, and clinical outcome in patients with severe sepsis

2014 ◽  
Vol 29 (5) ◽  
pp. 723-727 ◽  
Author(s):  
Alexandra Lekkou ◽  
Athanassia Mouzaki ◽  
Dimitrios Siagris ◽  
Ifigenia Ravani ◽  
Charalambos A. Gogos
Keyword(s):  
Severe Sepsis ◽  
Clinical Outcome ◽  
Lipid Profile ◽  
Serum Lipid ◽  
Cytokine Production ◽  
Serum Lipid Profile

Cytokine production and clinical and laboratory aspects of EBV-associated acute infectious mononucleosis in children

2021 ◽  
Vol 19 (1) ◽  
pp. 58-63
Author(s):  
J.-C. Khakizimana ◽  
◽  
V.N. Timchenko ◽  
V.P. Novikova ◽  
O.P. Gurina ◽  
...  
Keyword(s):  
Infectious Mononucleosis ◽  
Cytokine Production ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interferon Α ◽  
Acute Tonsillitis ◽  
Cervical Lymph Nodes ◽  
Group I ◽  
Tnf Α ◽  
Group Ii ◽  
Acute Infectious Mononucleosis

Objective. To analyze clinical and laboratory parameters, as well as the dynamics of cytokine production in children of different ages with acute infectious mononucleosis caused by Epstein-Barr virus (EBV mononucleosis). Patients and methods. We examined two groups of patients: group I included 20 children aged 1 to 7 years, whereas group II included 29 children aged 8 to 17 years. All study participants were tested in the acute phase of the disease and in early convalescence. We evaluated serum levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interferon-α (IFN-α) using enzyme-linked immunosorbent assay (ELISA) (standard Vektor-Best kits, Russia). Data analysis was performed using Microsoft Excel 2019 for Windows and IBM SPSS statistics; we applied the methods of non-parametric statistics. Differences were considered significant at p < 0.05. Results. The majority of children had fever, intoxication, acute tonsillitis, and enlarged cervical lymph nodes. Laboratory makers, such as lymphocytosis, neutropenia, and thrombocytopenia were more pronounced in children from group II. In both groups, the level of cytokines in the acute period of the disease was higher than the discriminatory one. In early convalescence, patients from group I demonstrated more significant reduction in the cytokine level than patients from group II (р < 0.05). In children over 7 years of age, the levels of IL-10 and TNF-α positively correlated with the disease duration (p < 0.01 and p < 0.05, respectively) Conclusion. The level of cytokine production in acute EBV mononucleosis depends on patients’ age. Concentrations of IL-10 and TNF-α can serve as markers reflecting the severity of EBV mononucleosis and can be used for disease prognosis. Key words: EBV mononucleosis, children, cytokines, IL-6, IL-10, TNF-α, IFN-α

LABOUR CONDITIONS AND POSSIBILITY OF APPLICATION OF ETHYLMETHYLHYDROXYPYRIDINE SUCCINATE IN WORKERS EXPOSED TO FIBROGENIC SILICATE DUST

2021 ◽  
Author(s):  
N.V. Shumatova ◽  
Keyword(s):  
Lipid Profile ◽  
Systemic Inflammation ◽  
Respiratory Function ◽  
Laboratory Parameters ◽  
Tnf Α ◽  
Partial Correction ◽  
Ethylmethylhydroxypyridine Succinate

Abstract. Labour conditions of workers contacting with fibrogenic silicate dust in isolators’ production were studied. Additional examination included determination of the degree of endothelial disfunction, apoptosis and systemic inflammation. Besides the effect of Ethylmethylhydroxypyridine succinate on these parameters and the lipid profile was evaluated. Atherogenic changes of the lipid profile, moderate endothelial disfunction (level of circulating endotheliocytes is 6,04±1,97*104/l), slight tension of apoptosis (TNF-α 8,11±6,67 pg/ml) and activation of systemic inflammation (C-RP 8,1±4,5 mg/l) were found. Application of Ethylmethylhydroxypyridine succinate led to the partial correction of dyslipidemia and endothelial disfunction without the significant effect on other researching laboratory parameters; significant improvement of respiratory function was noted.

scholarly journals Distinct PKC-mediated posttranscriptional events set cytokine production kinetics in CD8+ T cells

2017 ◽  
Vol 114 (36) ◽  
pp. 9677-9682 ◽  
Author(s):  
Fiamma Salerno ◽  
Nahuel A. Paolini ◽  
Regina Stark ◽  
Marieke von Lindern ◽  
Monika C. Wolkers
Keyword(s):  
T Cells ◽  
Mrna Stability ◽  
Cytokine Production ◽  
De Novo ◽  
Translation Efficiency ◽  
Mrna Stabilization ◽  
Relative Contribution ◽  
Production Kinetics ◽  
Tnf Α ◽  
Ifn Γ

Effective T cell responses against invading pathogens require the concerted production of three key cytokines: TNF-α, IFN-γ, and IL-2. The cytokines functionally synergize, but their production kinetics widely differ. How the differential timing of expression is regulated remains, however, poorly understood. We compared the relative contribution of transcription, mRNA stability, and translation efficiency on cytokine production in murine effector and memory CD8+ T cells. We show that the immediate and ample production of TNF-α is primarily mediated by translation of preformed mRNA through protein kinase C (PKC)-induced recruitment of mRNA to polyribosomes. Also, the initial production of IFN-γ uses translation of preformed mRNA. However, the magnitude and subsequent expression of IFN-γ, and of IL-2, depends on calcium-induced de novo transcription and PKC-dependent mRNA stabilization. In conclusion, PKC signaling modulates translation efficiency and mRNA stability in a transcript-specific manner. These cytokine-specific regulatory mechanisms guarantee that T cells produce ample amounts of cytokines shortly upon activation and for a limited time.

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