Inflammatory response to osmotic stimulus in healthy volunteers

2019 ◽  
Author(s):  
Clara O Sailer ◽  
Sophia Wiedemann ◽  
Wiebke K Fenske ◽  
Ingeborg Schnyder ◽  
Konrad Strauss ◽  
...  
2020 ◽  
Vol 27 (1) ◽  
pp. 16-24
Author(s):  
Marcelo G. Lima ◽  
Vitor S. Tardelli ◽  
Elisa Brietzke ◽  
Thiago M. Fidalgo

<b><i>Introduction:</i></b> Although the recreational cannabis use is expressive worldwide, the literature about medical potential of cannabis extracts, including its anti-inflammatory properties, remains inconclusive. <b><i>Methods:</i></b> We screened all articles, published on the PubMed database, on inflammatory mediators and any information about cannabis use from 1980 to March 2019. <b><i>Results:</i></b> Six studies were included, and the main findings were as follows: (i) among healthy volunteers and cannabis users, cannabinoids seemed to decrease the inflammatory response, thus decreasing the immune response, which led to a higher risk of infections; (ii) among patients with multiple sclerosis, cannabinoids seemed to have little impact on the inflammatory markers’ levels. <b><i>Discussion:</i></b> Although cannabis use can produce immune inflammatory suppression in healthy people, this effect is not robust enough to change inflammatory mediators’ levels in situations of highly dysfunctional inflammatory activation. Nevertheless, the impact of cannabinoids in clinical outcomes of these conditions remains to be determined.


2020 ◽  
Vol 66 (5) ◽  
pp. 411-418
Author(s):  
E.V. Mikhalchik ◽  
I.V. Borodina ◽  
I.V. Vlasova ◽  
T.V. Vakhrusheva ◽  
N.P. Gorbunov ◽  
...  

In cases of any acute surgical abdominal disease the progression of purulent inflammation can lead to local or diffuse peritonitis. The indicators of the degree and specificity of the inflammatory response in blood such as cytokine concentration, neutrophil activity, plasma antioxidant capacity (thiols concentration) could be considered as potential predictors of complications. The luminol-dependent chemiluminescence (CL) response of blood activated by the phorbol ester (PMA), and the concentration of cytokines IL-6, IL-8, IL-10, myeloperoxidase (MPO) and thiols in plasma were measured in patients with uncomplicated condition (group 1, n=8), local peritonitis (group 2, n=9) or diffuse peritonitis (group 3, n=9) at admission to surgery (before surgical operation, b/o), immediately after surgical operation (a/o) and a day after surgery (1 day) as well as in healthy volunteers (norm, n=12). In all time-points the cytokines and MPO concentrations measured by ELISA, in group 3 were higher than in healthy volunteers and in patients in groups 1 and 2. Blood CL demonstrated a more than 5-fold increase above the normal values in all patients, and was also higher in group 2 as compared to group 1 (b/o and a/o). Patients in group 3 had shown both maximum and minimum of CL values, which could be a consequence of neutrophil priming or exhaustion (“immune paralysis”), respectively. The same patients' plasma exhibited low thiol concentration (≤30% vs normal values). In patients with fatal outcomes (group 3, n=2) within a day after surgery, either a decrease of the CL to zero values concurrently with elevated IL-8 and IL-6 concentrations and low thiol levels was observed, or CL exceeded normal values more than 20 times with concurrent complete exhaustion of the plasma thiol pool. No clear dependency between the plasma parameters and neutrophil activity was found. Hence a parameter set for prognosis and/or early diagnosis of infectious complications in acute abdominal pathology should include different biomarkers of the inflammatory response: cytokine profile (IL-6, IL-8, IL-10), MPO and neutrophil activity, antioxidant plasma capacity (e.g., total thiols concentration).


2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Li ◽  
Qiang Wen ◽  
Huaisheng Chen ◽  
Xinhui Wu ◽  
Bin Liu ◽  
...  

The pathological mechanism underlying heat stroke (HS) is associated with the dysbalanced inflammation and coagulation cascade. Cell-derived circulating extracellular vesicles (EVs), as a novel pathway mediating intercellular communication, are associated with the immune response and inflammation in critical inflammatory syndromes, such as sepsis. Although these vesicles contain genetic material correlated with their biological function, their molecular cargo during HS remains unknown. In this study, we evaluate the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) associated with inflammatory responses and coagulation cascade in exosomes of patients with HS. Blood samples were collected from three patients with HS at the time of admission to the intensive care unit; three healthy volunteers were selected as control. Exosomes were isolated using ultracentrifugation, and their miRNA content was profiled using next-generation sequencing; mRNA content was evaluated using qPCR array. Compared with those from healthy volunteers, exosomes from patients with HS showed substantial changes in the expression of 202 exosomal miRNAs (154 upregulated and 48 downregulated miRNAs). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290, and let7-5p, whereas the most downregulated ones included miR-150-3p, 146a-5p, and 151a-3p. Gene ontology enrichment of the miRNAs of patients with HS compared with control subjects were associated mostly with inflammatory response, including T cell activation, B cell receptor signaling, dendritic cell chemotaxis and leukocyte migration, and platelet activation and blood coagulation. The identified miRNAs were primarily enriched to the signal transduction pathways namely, T cell receptor signaling, Ras signaling, chemokine signaling, platelet activation, and leukocyte transendothelial migration, all of which are associated with inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation, and platelet activation were further verified in serum exosomes. Exosomes from patients with HS convey miRNAs and mRNAs associated with pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during HS.


2005 ◽  
Vol 11 (4) ◽  
pp. 207-212 ◽  
Author(s):  
Robert C.M. Stephens ◽  
Catherine M.N. O'Malley ◽  
Robert J. Frumento ◽  
Michael G. Mythen ◽  
Elliott Bennett-Guerrero

2019 ◽  
Vol 8 (9) ◽  
pp. 1282-1287
Author(s):  
Clara Odilia Sailer ◽  
Sophia Julia Wiedemann ◽  
Konrad Strauss ◽  
Ingeborg Schnyder ◽  
Wiebke Kristin Fenske ◽  
...  

Osmotic stimulus or stress results in vasopressin release. Animal and human in vitro studies have shown that inflammatory parameters, such as interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α), increase in parallel in the central nervous system and bronchial, corneal or intestinal epithelial cell lines in response to osmotic stimulus. Whether osmotic stimulus directly causes a systemic inflammatory response in humans is unknown. We therefore investigated the influence of osmotic stimulus on circulatory markers of systemic inflammation in healthy volunteers. In this prospective cohort study, 44 healthy volunteers underwent a standardized test protocol with an osmotic stimulus leading into the hyperosmotic/hypernatremic range (serum sodium ≥150 mmol/L) by hypertonic saline infusion. Copeptin – a marker indicating vasopressin activity – serum sodium and osmolality, plasma IL-8 and TNF-α were measured at baseline and directly after osmotic stimulus. Median (range) serum sodium increased from 141 mmol/L (136, 147) to 151 mmol/L (145, 154) (P < 0.01), serum osmolality increased from 295 mmol/L (281, 306) to 315 mmol/L (304, 325) (P < 0.01). Median (range) copeptin increased from 4.3 pg/L (1.1, 21.4) to 28.8 pg/L (19.9, 43.4) (P < 0.01). Median (range) IL-8 levels showed a trend to decrease from 0.79 pg/mL (0.37, 1.6) to 0.7 pg/mL (0.4, 1.9) (P < 0.09) and TNF-α levels decreased from 0.53 pg/mL (0.11, 1.1) to 0.45 pg/mL (0.12, 0.97) (P < 0.036). Contrary to data obtained in vitro, circulating proinflammatory cytokines tend to or decrease in human plasma after osmotic stimulus. In this study, osmotic stimulus does not increase circulating markers of systemic inflammation.


2021 ◽  
Vol 10 (3) ◽  
pp. 511-520
Author(s):  
O. A. Grebenchikov ◽  
A. K. Shabanov ◽  
L. L. Nikolayev ◽  
A. I. Shpichko ◽  
I. V. Bratishchev ◽  
...  

Background. The syndrome of systemic inflammatory response, which underlies the damaging effect of factors of infectious and non-infectious genesis, may cause multiple organ failure. The degree of its severity is determined, among other things, by the activation of neutrophils. The paper highlights new mechanisms of the anti-inflammatory action of the inhalation anesthetic xenon, mediated by a decrease in the ability of neutrophils to pro-inflammatory response.Aim of study. To evaluate the effect of xenon on the activation of human neutrophils under ex vivo conditions.Material AND methods. We studied the effect of xenon inhalation on reduction of the ability of neutrophils to be activated proinflammatory by reduced expression of adhesion molecules CD11b and CD66b on the surface of neutrophils and on the phosphorylation of proinflammatory kinases: ERK 1/2 and kinase — p38 in neutrophils of healthy volunteers.Results. The use of xenon at a dose of 30 vol. % within 60 minutes in healthy volunteers statistically significantly reduces the ability of neutrophils to proinflammatory activation. The addition of lipopolysaccharide (LPS) to the incubation medium of neutrophils causes their pronounced activation, statistically significantly increasing the phosphorylation of key proinflammatory neutrophil kinases ERK1/2 and kinase p38. Inhalation of xenon in volunteers (30% within 60 minutes) has a pronounced anti-inflammatory effect on LPS-stimulated neutrophils, decreasing their activation by inhibiting pro-inflammatory kinase ERK1/2 and pro-inflammatory MAP kinase p38.Conclusion. The actual study, performed on isolated neutrophils from volunteers who underwent xenon inhalation, revealed the anti-inflammatory properties of the inert gas xenon, which, in our opinion, may have a direct relationship to the identification of the mechanism of its neuroprotective properties. Thus, the research results available today suggest that xenon has a pronounced pleiotropic mechanism of brain protection. This is a partial blockade of NMDA receptors, and phosphorylation of the enzyme glycogen synthase-3β, and limitation of the inflammatory activation of neutrophils.Findings. Inhalation of xenon in volunteers (30% within 60 minutes) has a pronounced anti-inflammatory effect on neutrophils stimulated by lipopolysaccharides, decreasing their activation by inhibiting proinflammatory ERK 1/2 kinase and proinflammatory MAP kinase p38, as well as reducing the expression of markers of activation and degranulation CD11b and CD66b on the surface of neutrophils. Stimulation by lipopolysaccharides statistically significantly reduces spontaneous apoptosis of neutrophils, while xenon increases the ability of neutrophils to apoptosis, which is likely to contribute to the resolution of inflammation.


2020 ◽  
Author(s):  
Yue Li ◽  
Qiang Wen ◽  
Huaisheng Chen ◽  
Xinhui Wu ◽  
Bin Liu ◽  
...  

Abstract Background: The pathological mechanism of HS is associated with the dysbalanced inflammation and coagulation cascade. The cells-derived circulating extracellular vesicles (EVs) as a novel pathway mediating intercellular communication were evidenced to be associated with immune response and inflammation in critical inflammatory syndromes such as sepsis. Despite previous studies demonstrating that these vesicles contain genetic material related to their biological function, their molecular cargo during heat stroke is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and coagulation cascade in exosomes of patients with heat stroke. Methods: Blood samples were collected from 3 patients with heat stroke at ICU admission. Three healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, their miRNA content was profiled by next generation sequencing and mRNA content was evaluated by qRT-PCR array. Results: As compared with healthy volunteers, exosomes from patients with heat stroke had significant changes in 202 exosomal miRNAs (154 miRNAs upregulated and 48 downregulated). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290 and let7-5p whileas the most downregulated ones included miR-150-3p, 146a-5p and 151a-3p. The GO enrichment by the miRNAs of patients with heat stroke compared with control subjects were related mostly to inflammatory response including T cell activation, B cell receptor signaling, DC chemotaxis and leukocyte migration, and platelet activation and blood coagulation. KEGG pathway analysis determined those identified miRNAs were mainly enriched to the signal transduction pathways namely, T cell receptor signaling pathway, Ras signaling pathway, Chemokine signaling pathway, Platelet activation, and Leukocyte transendothelial migration. These pathways were mainly related to inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation and platelet activation were further verified in serum exosomes.Conclusions: Exosomes from patients with heat stroke convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during heat stroke.


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