Alcoholization and ethanol withdrawal leads to the activation of neuroimmune response in the prefrontal rat brain

2019 ◽  
Vol 65 (5) ◽  
pp. 380-384
Author(s):  
M.I. Airapetov ◽  
S.O. Eresko ◽  
A.A. Lebedev ◽  
E.R. Bychkov ◽  
P.D. Shabanov
Keyword(s):  
Ethanol Withdrawal ◽  
Ethanol Administration ◽  
Control Group ◽  
Prolonged Administration ◽  
Hmgb1 Protein ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Chronic Ethanol Administration ◽  
The Brain ◽  
Pro Inflammatory Cytokines

The effects of acute (single) and chronic ethanol administration on the level of pro-inflammatory cytokines (IL-1β and TNF-α), as well as on the level of mRNA NF-κB, TLR4 and its endogenous agonist, HMGB1 protein, were investigated in rats. It was shown that the level of TLR4, HMGB1 and cytokines was significantly higher than in control group. The ethanol withdrawal after prolonged administration resulted in dysregulation of cytokine levels, TLR4 and HMGB1. Changes in the level of TLR4 and HMGB1 mRNA demonstrated a similar pattern. The obtained data confirm that prolonged alcoholization leads to the activation of TLR4-dependent signaling in the prefrontal cortex of rats, and this can lead to a prolonged neuro-inflammatory process in the brain.

Evaluation of Inflammatory Biomarkers in Iranian Patients with Cystic Fibrosis

2020 ◽  
Vol 16 ◽  
Author(s):  
Hosseinali Ghaffaripour ◽  
Mohammadreza Mirkarimi ◽  
Maryam Hassanzad ◽  
Mohammadreza Boloursaz ◽  
Shooka Mohammadi
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Control Group ◽  
Respiratory Dysfunction ◽  
Three Samples ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Before And After ◽  
The Mean ◽  
Pro Inflammatory Cytokines

Background:: Cystic fibrosis (CF) is an autosomal recessive disease, characterized by progressive and recurrent lung infection. Objective:: This study aimed to evaluate the levels of pro-inflammatory cytokines and their correlations with lung function in CF patients. Methods:: Methods: Results:: The mean age of CF patients was 15.43 ± 5.970 years (range 4-24). The FVC in a majority of the CF patients (66.7%) was below 60% and only 33.3% of the patients exhibited normal or mild respiratory dysfunction. There were significant differences between FVC and FEV1 measurements before and after bronchoscopy. In addition, IL-8 levels in all three samples (serum, sputum, and BAL) of CF patients and levels of IL-1β and TNF-α in BAL and sputum samples of CF patients were significantly higher than the control group (p<0.001). However, increased cytokine levels were not associated with lung function. Conclusion:: Increased IL-8 and TNF-α levels seemed to be associated with signs of clinical deterioration and might be useful as diagnostic markers.

scholarly journals Inhibition of rat brain tryptophan metabolism by ethanol withdrawal and possible involvement of the enhanced liver tryptophan pyrrolase activity

1980 ◽  
Vol 192 (2) ◽  
pp. 449-455 ◽  
Author(s):  
A A B Badawy ◽  
N F Punjani ◽  
C M Evans ◽  
M Evans
Keyword(s):  
Rat Brain ◽  
Ethanol Withdrawal ◽  
Chronic Ethanol ◽  
Tryptophan Metabolism ◽  
Ethanol Administration ◽  
Time Intervals ◽  
Chronic Ethanol Administration ◽  
Tryptophan Pyrrolase ◽  
The Brain ◽  
Withdrawal Phase

1. Chronic ethanol administration to rats was previously shown to enhance brain 5-hydroxytryptamine synthesis by increasing the availability of circulating tryptophan to the brain secondarily to the NAD(P)H-mediated inhibition of liver tryptophan pyrrolase activity. 2. At 24h after ethanol withdrawal, all the above effects were observed because liver [NAD(P)H] was still increased. By contrast, all aspects of liver and brain tryptophan metabolism were normal at 12 days after withdrawal. 3. At 7–9 days after withdrawal, brain 5-hydroxytryptamine synthesis was decreased, as was tryptophan availability to the brain. Liver tryptophan pyrrolase activity at these time-intervals was maximally enhanced. 4. Administration of nicotinamide during the withdrawal phase not only abolished the withdrawal-induced enhancement of tryptophan pyrrolase activity on day 8, but also maintained the inhibition previously caused by ethanol. Under these conditions, the withdrawal-induced decreases in brain 5-hydroxytryptamine synthesis and tryptophan availability to the brain were abolished, and both functions were enhanced. Nicotinamide alone exerted similar effects in control rats. 5. It is suggested that ethanol withdrawal inhibits brain 5-hydroxytryptamine synthesis by decreasing tryptophan availability to the brain secondarily to the enhanced liver tryptophan pyrrolase activity. 6. The results are discussed in relation to the possible involvement of 5-hydroxytryptamine in dependence on ethanol and other drugs.

scholarly journals Tocilizumab-induced unexpected increase of several inflammatory cytokines in critically ill COVID-19 patients

2021 ◽  
Author(s):  
Fanny Ponthieux ◽  
Nicolas Dauby ◽  
Evelyne Maillart ◽  
Jean-François Fils ◽  
Julie Smet ◽  
...  
Keyword(s):  
Critically Ill ◽  
Inflammatory Cytokines ◽  
Control Group ◽  
Serum Samples ◽  
Off Label ◽  
Tnf Α ◽  
Significant Difference ◽  
Cytokine Levels ◽  
Pro Inflammatory Cytokines

Abstract Early evidence during the COVID-19 pandemic indicated high levels of IL-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic.We aimed to monitor IL-6 and several inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Fifteen critically ill SARS-CoV-2 PCR confirmed cases were enrolled and serum samples were collected during 8 days, before and following administration of a single dose of TCZ. In parallel, a control group consisting of 8 non-treated COVID-19 patients not receiving TCZ was established. Serum profile of 12 cytokines (IL-1β, -2, -4, -6, -8, -10, -12, -13, -17, -18, TNF-α and INF-γ) and of IL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1β, -2, -4, -10, -12p70, -18 and IL-6R levels in the treated patients with maximal values reached 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. There was no significant difference in cytokine levels between survivors (TCZ/S) or non-survivors (TCZ/D). This observation suggests that some inflammatory pathways escape IL-6R blockade leading to an increase in several pro-inflammatory cytokines. Our findings could highlight an anti-inflammatory role of IL-6 and may explain why TCZ has failed to improve survival in critically ill COVID-19 patients when given alone.

scholarly journals Inhibition of Leukocyte Entry into the Brain by the Selectin Blocker Fucoidin Decreases Interleukin-1 (IL-1) Levels but Increases IL-8 Levels in Cerebrospinal Fluid during Experimental Pneumococcal Meningitis in Rabbits

2000 ◽  
Vol 68 (6) ◽  
pp. 3153-3157 ◽  
Author(s):  
Christian Østergaard ◽  
Runa Vavia Yieng-Kow ◽  
Thomas Benfield ◽  
Niels Frimodt-Møller ◽  
Frank Espersen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Pneumococcal Meningitis ◽  
Interleukin 1 ◽  
Treated Group ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Significant Difference ◽  
The Brain ◽  
Experimental Pneumococcal Meningitis

ABSTRACT The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rabbits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of ∼106 CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7). CSF samples were obtained every second hour during a 16-h study period. Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively;P < 0.02). A less consistent decrease in CSF TNF-α levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels. Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively;P < 0.09). In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-α into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.

scholarly journals Analysis of the physical activity effects and measurement of pro-inflammatory cytokines in irradiated lungs in rats

2012 ◽  
Vol 27 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Renata Cristiane Gennari Bianchi ◽  
Eduardo Rochete Ropelle ◽  
Carlos Kiyoshi Katashima ◽  
José Barreto Campello Carvalheira ◽  
Luiz Roberto Lopes ◽  
...  
Keyword(s):  
Physical Activity ◽  
Western Blotting ◽  
Inflammatory Cytokines ◽  
Lower Lobe ◽  
Whole Body ◽  
Control Group ◽  
Western Blotting Analysis ◽  
Blotting Analysis ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

PURPOSE: To study if the pre-radiotherapy physical activity has radio-protective elements, by measuring the radio-induced activation of pro-inflammatory cytokines as interleukin-6 (il-6), transforming growth factor -β (tgf -β), tumor necrosis factor -α (tnf-α) and protein beta kinase β (ikkβ), through western blotting analysis. METHODS: A randomized study with 28 Wistar hannover rats, males, with a mean age of 90 days and weighing about 200 grams. The animals were divided into three groups: (GI, GII and GIII). GIII group were submitted to swimming for eight weeks (zero load, three times a week, about 30 minutes). Then, the groups (except the control group) were submitted to irradiation by cobalt therapy, single dose of 3.5 gray in the whole body. All animals were sacrificed by overdose of pentobarbital, according to the time for analysis of cytokines, and then a fragment of the lower lobe of the right lung went to western blotting analysis. RESULTS: The cytokines IKK β, TNF-α and IL-6 induced by radiation in the lung were lower in the exercised animals. However, exercise did not alter the radiation-induced increase in tgf-β. CONCLUSION: The results show a lower response in relation to inflammatory cytokines in the group that practiced the exercise pre-radiotherapy, showing that exercise can protect tissues from tissue damage due to irradiation.

scholarly journals Clozapine Prevents Poly (I:C) Induced Inflammation by Modulating NLRP3 Pathway in Microglial Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 577
Author(s):  
Vijayasree V. Giridharan ◽  
Giselli Scaini ◽  
Gabriela D. Colpo ◽  
Tejaswini Doifode ◽  
Omar F. Pinjari ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Nlrp3 Inflammasome ◽  
Antipsychotic Drugs ◽  
Poly I:C ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Primary Microglial Cell ◽  
Anti Inflammatory ◽  
The Brain ◽  
Nlrp3 Expression

Schizophrenia is a complex psychiatric disorder that exhibits an interconnection between the immune system and the brain. Experimental and clinical studies have suggested the presence of neuroinflammation in schizophrenia. In the present study, the effect of antipsychotic drugs, including clozapine, risperidone, and haloperidol (10, 20 and 20 μM, respectively), on the production of IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, IL-18, INF-γ, and TNF-α was investigated in the unstimulated and polyriboinosinic-polyribocytidilic acid [poly (I:C)]-stimulated primary microglial cell cultures. In the unstimulated cultures, clozapine, risperidone, and haloperidol did not influence the cytokine levels. Nevertheless, in cell cultures under strong inflammatory activation by poly (I:C), clozapine reduced the levels of IL-1α, IL-1β, IL-2, and IL-17. Risperidone and haloperidol both reduced the levels of IL-1α, IL-1β, IL-2, and IL-17, and increased the levels of IL-6, IL-10, INF-γ, and TNF-α. Based on the results that were obtained with the antipsychotic drugs and observing that clozapine presented with a more significant anti-inflammatory effect, clozapine was selected for the subsequent experiments. We compared the profile of cytokine suppression obtained with the use of NLRP3 inflammasome inhibitor, CRID3 to that obtained with clozapine, to test our hypothesis that clozapine inhibits the NLRP3 inflammasome. Clozapine and CRID3 both reduced the IL-1α, IL-1β, IL-2, and IL-17 levels. Clozapine reduced the level of poly (I:C)-activated NLRP3 expression by 57%, which was higher than the reduction thay was seen with CRID3 treatment (45%). These results suggest that clozapine might exhibit anti-inflammatory effects by inhibiting NLRP3 inflammasome and this activity is not typical with the use of other antipsychotic drugs under the conditions of strong microglial activation.

scholarly journals Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

2021 ◽  
Vol 18 (16) ◽  
pp. 8538
Author(s):  
Maciej Kwiatek ◽  
Tomasz Gęca ◽  
Anna Kwaśniewska
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Control Group ◽  
Study Group ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

scholarly journals The expression and significance of inflammatory cytokines and MMP-9 in the tears of the infected eye and contralateral uninfected eye in patients with fungal keratitis

2021 ◽  
Author(s):  
Shuang Zhang ◽  
Hui-Min Wu ◽  
Xiang-Ni Cao ◽  
Xian-Qi Zhang ◽  
Gui-ping Gao
Keyword(s):  
Tear Film ◽  
Fungal Keratitis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Healthy Controls ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Healthy Control ◽  
The Relationship ◽  
Tear Film Function

Abstract Background: We investigated bilateral tear cytokine levels including interleukin (IL)-1β, IL-10, IL-17, tumor necrosis factor (TNF)-α and Matrix metalloproteinase-9 (MMP-9) in patients with fungal keratitis(FK). Meanwhile, we evaluated the relationship between the changes of tear cytokines with corneal perception and pain in infected eyes, and the relationship between tear cytokines and tear film function in contralateral uninfected eyes .Methods : A total of 60(20 FK, 20 contralateral, 20 healthy controls) tear samples were collected prospectively and analyzed by enzyme linked immunosorbent assay(ELISA). Approximately 50 to 60 ul of tear samples in each case were collected. Meanwhile ,we analyzed the changes of visual analogue scale(VAS), tear breakup time (TBUT), Schirmer I test (SIT) and corneal perception compared with healthy controls. Results :The concentrations of IL-1β, IL-10 and IL-17 increased in bilateral eyes compared with healthy controls(P<0.05). The tear concentrations of MMP-9 , TNF-α only significantly increased in affected eyes (P <0.05). Patients with FK showed significant reduction in corneal perception of infected eyes compared with controls(P<0.05). Corneal perception of the normal eyes in FK patients was slightly lower than that of control group, but there was not statistical difference (P>0.05).TBUT and SIT of contralateral uninfected eyes were significantly lower than that of control group(P<0.05), which were significantly correlated with levels of IL-1β, IL-17(P<0.05). SIT were also negatively correlated with MMP-9(P<0.05), while the levels of IL-1β, IL-10, IL-17, TNF-α and MMP-9 in the tears of the healthy control group had no significant correlation with TBUT and SIT indicators(P>0.05).The corneal perception and VAS score of the affected FK eyes showed correlation with IL-1β, IL-17 and TNF-α(P<0.05).In addition, concentration of IL-10 inversely was correlated with VAS (P<0.05). Conclusion: Proinflammatory tear cytokines are elevated in bilateral eyes with unilateral FK as associated with tear film function ,pain and corneal sensitivity.

scholarly journals Rosiglitazone Decreases Serum Bone-Specific Alkaline Phosphatase Activity in Postmenopausal Diabetic Women

2007 ◽  
Vol 92 (9) ◽  
pp. 3523-3530 ◽  
Author(s):  
Zehra Berberoglu ◽  
Alptekin Gursoy ◽  
Nilufer Bayraktar ◽  
Ayse Canan Yazici ◽  
Neslihan Bascil Tutuncu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Controlled Trial ◽  
Lifestyle Changes ◽  
Control Group ◽  
Long Term Effects ◽  
Open Label ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Rosiglitazone Treatment

Abstract Objectives: Our objectives were to evaluate the effect of rosiglitazone on bone metabolism and to assess the association between changes in bone turnover parameters and plasma cytokine levels in postmenopausal diabetic women. Design: This was a 12-wk open-label randomized-controlled trial. Patients or Other Participants: A total of 56 obese postmenopausal women with newly diagnosed diabetes and 26 nondiabetic healthy controls matched for age and body mass index were included in the study. Interventions: The subjects were instructed to follow a weight-maintenance diet. Half were randomly assigned to receive rosiglitazone 4 mg/d, and the other half remained on diet alone. Main Outcome Measures: Before and after the interventions, metabolic bone markers and serum cytokine levels were assessed. Results: Serum total alkaline phosphatase (ALP) and bone-specific ALP levels were statistically significantly lower 12 wk after initiation of rosiglitazone treatment. There were no statistically significant changes in osteocalcin levels among the three groups or in deoxypyridinoline levels in the rosiglitazone group. At the end of 12 wk, all patients had statistically significantly decreased IL-1β and TNF-α levels compared with baseline. Changes in bone-specific ALP levels showed a moderate negative correlation with the changes in the TNF-α levels after rosiglitazone treatment and after diet in the diabetic control group. Conclusions: Rosiglitazone use is associated with reduced bone formation at earlier stages in postmenopausal diabetic women. The cytokine-lowering effects of rosiglitazone and lifestyle changes could reverse the early inhibitory effect of rosiglitazone therapy on bone formation. Further studies will clarify the long-term effects of rosiglitazone therapy on bone loss and fracture.

Cytokine Levels in Critically Ill Children With Severe Sepsis and Their Relation With the Severity of Illness and Mortality

2020 ◽  
pp. 088506662091298
Author(s):  
Suresh Kumar Angurana ◽  
Arun Bansal ◽  
Jayashree Muralidharan ◽  
Ritu Aggarwal ◽  
Sunit Singhi
Keyword(s):  
Severe Sepsis ◽  
Critically Ill ◽  
Inflammatory Cytokines ◽  
Severity Of Illness ◽  
Critically Ill Children ◽  
Positive Correlation ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Objective: To study the baseline cytokine levels and their relation with the severity of illness and mortality in critically ill children with severe sepsis. Design: Subgroup analysis of a randomized, double-blind, placebo-controlled trial. Setting: Pediatric intensive care unit of a tertiary level teaching hospital in India. Patients: Fifty children with severe sepsis aged 3 months to 12 years. Material and Methods: Blood was collected at admission for estimation of pro-inflammatory (interleukin 6 [IL-6], IL-12p70, IL-17, and tumor necrotic factor α [TNF-α]) and anti-inflammatory (IL-10 and transforming growth factor β1 [TGF-β1]) cytokines. Primary Outcome: To find out correlation between cytokine levels and severity of illness scores (Pediatric Risk of Mortality [PRISM] III score, Sequential Organ Failure Assessment [SOFA], and Vasoactive-Inotropic Score [VIS]). Secondary Outcomes: To compare cytokine levels among survivors and nonsurvivors. Results: Baseline pro-inflammatory cytokine levels (median [interquartile range]) were IL-6: 189 (35-285) pg/mL, IL-12p: 48 (28-98) pg/mL, IL-17: 240 (133-345) pg/mL, and TNF-α: 296 (198-430) pg/mL; anti-inflammatory cytokine levels were IL-10: 185 (62-395) pg/mL and TGF-β1: 204 (92-290) ng/mL. Pro-inflammatory cytokines showed positive correlation with PRISM III score: IL-6 (Spearman correlation coefficient, ρ = 0.273, P = .06), IL-12 (ρ = 0.367, P = .01), IL-17 (ρ = 0.197, P = .17), and TNF-α (ρ = 0.284, P = .05), and anti-inflammatory cytokines showed negative correlation: IL-10 (ρ = −0.257, P = .09) and TGF-β (ρ = −0.238, P = .11). Both SOFA and VIS also showed weak positive correlation with IL-12 (ρ = 0.32, P = .03 and ρ = 0.31, P = .03, respectively). Among nonsurvivors (n = 5), the levels of all the measured pro-inflammatory cytokines were significantly higher as compared to survivors, IL-6: 359 (251-499) pg/mL versus 157 (97-223) pg/mL, P < .0001, IL-12p70: 167 (133-196) pg/mL versus 66 (30-100) pg/mL, P < .0001, IL-17: 400 (333-563) pg/mL versus 237 (122-318) pg/mL, P = .009, and TNF-α: 409 (355-503) pg/mL versus 330 (198-415) pg/mL, P = .002, respectively. Conclusion: In critically ill children with severe sepsis, pro-inflammatory cytokines (especially IL-12p70) showed a weak positive correlation with severity of illness and were significantly higher among nonsurvivors.

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