Significance of the determination of proinflammatory cytokines in the serum of polytraumatized patients with sepsis

Severe sepsis and trauma complicated with multiple organ dysfunction syndrome (MODS) are among the leading causes of death in intensive therapy units with mortality rate exceeding 50%. The outcome is not determined only by infection or trauma, but also by the intensity of immuno-inflammatory response, which is essential for host defence, but if uncontrolled leads to MODS. Pro-inflammatory cytokines (tumor necrosis factor-a -TNF-a, IL-1 IL-8, IL-12, IFN-g, etc) represent a part of this immuno-inflammatory response to an insult. The results of the clinical investigation of correlation between pro-inflammatory cytokines (IL-8, IL-12, TNF-a, IFN-g) the outcome (survivors, non-survivors), and the severity (systemic inflammatory response syndrome - SIRS - less severe, and MODS - more severe) in polytraumatised patients with sepsis are presented in this paper. Mean values of IL-8 were 1.3-fold higher in non-survivors (p<0.05), and 60-fold higher in MODS group (p<0.01). Mean values of IL-12 were 1.6-fold higher in survivors (p<0.01), while the values between SIRS and MODS group did not differ significantly; mean values of TNF-a were 3-fold higher in survivors (p<0.05), and 46-fold higher in MODS group (p<0.01). Mean values of IFN-g did not differ significantly between the two groups regarding the outcome and severity. The obtained results indicated that IL-8 was a reliable predictor of lethal outcome and MODS (p<0.01), IL-12 a reliable predictor of survival (p<0.05), and TNF-a a reliable predictor of survival (p<0.05) and MODS (p<0.01).

Download Full-text

Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

Scientific Reports ◽

10.1038/s41598-021-93064-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Awadhesh K. Arya ◽

Kurt Hu ◽

Lalita Subedi ◽

Tieluo Li ◽

Bingren Hu

Keyword(s):

Inflammatory Response ◽

Inflammatory Cytokines ◽

Troponin I ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Balloon Catheter ◽

Organ Injury ◽

Upper Body ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

AbstractResuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

Download Full-text

The Protective Effect of Picroside II on Isoflurane-Induced Neuronal Injury in Rats via Downregulating miR-195

NeuroImmunoModulation ◽

10.1159/000519779 ◽

2021 ◽

pp. 1-9

Author(s):

Hui Li ◽

Weijia Du ◽

Yawei Yuan ◽

Jingjing Xue ◽

Qiang Li ◽

...

Keyword(s):

Inflammatory Response ◽

Protective Effect ◽

Inflammatory Cytokines ◽

Escape Latency ◽

Neuronal Cells ◽

Neuronal Injury ◽

Morris Water Maze Test ◽

Picroside Ii ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Introduction: Numerous pieces of evidence demonstrated that isoflurane induces hippocampal cell injury and cognitive impairments. Picroside II has been investigated for its anti-apoptosis and antioxidant neuroprotective effects. We aimed to explore the protective effects of picroside II and the role of microRNA-195 (miR-195) on isoflurane-induced neuronal injury in rats. Methods: The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding escape latency and time in quadrant parameters. Real-time quantitative PCR was used to detect the expression levels of miR-195 and pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA, in the hippocampal tissues and neuronal cells. Results: The picroside II significantly improves isoflurane-induced higher escape latency and lower time spent in the quadrant compared with the control rats. Picroside II also promotes cell viability and suppresses cell apoptosis of isoflurane-induced neuronal cells. Besides, picroside II suppresses the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and miR-195 in vivo and in vitro. Furthermore, overexpression of miR-195 abrogates the effects of picroside II on the expression of pro-inflammatory cytokines. The appropriate dose of picroside II is 20 mg/kg. Conclusion: Picroside II could protect the nervous system possibly through inhibiting the inflammatory response in the isoflurane-induced neuronal injury of rats. The protective effect of picroside II may be achieved by downregulating the expression of miR-195 and then inhibiting the inflammatory response.

Download Full-text

IRF5 is increased in labouring myometrium and regulates pro-labour mediators

Reproduction ◽

10.1530/rep-18-0140 ◽

2018 ◽

Vol 156 (3) ◽

pp. 207-218

Author(s):

Ratana Lim ◽

Gillian Barker ◽

Martha Lappas

Keyword(s):

Preterm Birth ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Treatment Options ◽

Adult Life ◽

Human Myometrium ◽

Myometrial Cells ◽

Associated Proteins ◽

Term Labour ◽

Pro Inflammatory Cytokines

Preterm birth continues to be the leading cause of neonatal mortality and morbidities that can extend into adult life. Few treatment options stem from our incomplete understanding of the mechanisms of human labour and delivery. Activation of the inflammatory response in gestational tissues by inflammation and/or infection leads to the production of pro-inflammatory and pro-labour mediators, thus preterm birth. Interferon regulatory factor 5 (IRF5) has recently emerged as an important pro-inflammatory transcription factor involved in acute and chronic inflammation. The aims of this study were to determine the expression of IRF5 in human myometrium from labouring and non-labouring women, and whether IRF5 is involved in the genesis of pro-inflammatory and pro-labour mediators induced by pro-inflammatory cytokines or toll-like receptor (TLR) ligands. IRF5 mRNA and protein expression was significantly higher in human myometrium after spontaneous term labour, compared to non-labouring tissues. IRF5 mRNA expression was also significantly higher in primary myometrial cells treated with the pro-inflammatory cytokines IL1B or TNF. In primary myometrial cells, IRF5 knockdown by siRNA (siIRF5) was associated with significantly decreased expression and or secretion of pro-inflammatory cytokines (IL1A, IL6), chemokines (CXCL8, CCL2), adhesion molecules (ICAM1, VCAM1) and contraction-associated proteins PTGS2, PGF2α and PTGFR when in the presence of IL1B, TNF, fsl-1 (TLR2/6 ligand) or flagellin (TLR5 ligand). siIRF5-transfected cells also displayed decreased NF-κB RELA transcriptional activity in the presence of these preterm birth mediators. Our study suggests a novel role for IRF5 in the regulation of the inflammatory response in human myometrium.

Download Full-text

Sudachinoid- and Ichangensin-Type Limonoids from Citrus junos Downregulate Pro-Inflammatory Cytokines

International Journal of Molecular Sciences ◽

10.3390/ijms21186963 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6963

Author(s):

Jihun Shin ◽

Hwa Young Song ◽

Mina Lee

Keyword(s):

Inflammatory Cytokines ◽

Human Colon ◽

Dominant Group ◽

Citrus Junos ◽

Mouse Macrophages ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor ◽

Pro Inflammatory Cytokines

Limonoids, a dominant group of phytochemicals in the Rutaceae family, are known to exhibit several pharmacological activities. To identify natural products having efficacy against inflammatory bowel disease (IBD), we isolated 13 limonoids including a new compound, methyl sudachinoid A, from the seeds of Citrus junos and investigated their anti-inflammatory effects by assessing the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages and HT-29 human colon epithelial cells. Our findings revealed that limonoids significantly downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and nuclear transcription factor κB. In particular, sudachinoid-type compounds, methyl sudachinoid A and sudachinoid B, and ichangensin-type compound, 1-O-methyichangensin downregulated the expression of pro-inflammatory cytokines more potently than other limonoids, nomilin and limonin, which have been previously reported to exhibit anti-inflammatory activities in other cells; nomilin and limonin were therefore employed as positive controls in this study. Herein, we reveal that the anti-inflammatory activities of limonoids including a new compound methyl sudachinoid A from C. junos were mediated via the downregulation of pro-inflammatory cytokines and these limonoids can be employed as potential therapeutic phytochemicals for IBD.

Download Full-text

A pronounced uterine pro-inflammatory response at parturition is an ancient feature in mammals

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2017.1694 ◽

2017 ◽

Vol 284 (1865) ◽

pp. 20171694 ◽

Cited By ~ 11

Author(s):

Victoria L. Hansen ◽

Lauren S. Faber ◽

Ali A. Salehpoor ◽

Robert D. Miller

Keyword(s):

Immune System ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Immune Regulation ◽

Monodelphis Domestica ◽

Immune Gene ◽

Invasive Placenta ◽

Gene Transcripts ◽

Pro Inflammatory Cytokines

Regulating maternal immunity is necessary for successful human pregnancy. Whether this is needed in mammals with less invasive placentation is subject to debate. Indeed, the short gestation times in marsupials have been hypothesized to be due to a lack of immune regulation during pregnancy. Alternatively, the maternal marsupial immune system may be unstimulated in the absence of a highly invasive placenta. Transcripts encoding pro-inflammatory cytokines were found to be overrepresented in the whole uterine transcriptome at terminal pregnancy in the opossum, Monodelphis domestica . To investigate this further, immune gene transcripts were quantified throughout opossum gestation. Transcripts encoding pro-inflammatory cytokines remained relatively low during pre- and peri-attachment pregnancy stages. Levels dramatically increased late in gestation, peaking within 12 h prior to parturition. These results mirror the spike of inflammation seen at eutherian parturition but not at attachment or implantation. Our results are consistent with the role of pro-inflammatory cytokines at parturition being an ancient and conserved birth mechanism in therian mammals.

Download Full-text

Along a TNF-paved road from dead parasites in red cells to cerebral malaria, and beyond

Parasitology ◽

10.1017/s0031182009006088 ◽

2009 ◽

Vol 136 (12) ◽

pp. 1457-1468 ◽

Cited By ~ 9

Author(s):

I. A. CLARK

Keyword(s):

Inflammatory Cytokines ◽

Tumour Necrosis ◽

Personal Account ◽

Disease Pathogenesis ◽

Host Origin ◽

Paved Road ◽

Fresh Insight ◽

Insight Into ◽

Necrosis Factor ◽

Pro Inflammatory Cytokines

SUMMARYThis is a personal account of how tumour necrosis factor (TNF) the prototype of a group of host-origin mediators, often known as pro-inflammatory cytokines, came into parasitology, and was subsequently realised to be central to the pathogenesis of most disease pathology. This contribution summarizes an example of how a curiosity-driven outsider, with initially no intention of heading this way, and no relevant experience, and with no more than the simplest of plans but an ambition to read as widely as it takes, and (most importantly) allowed to follow his head, can be what is required to give fresh insight into understanding a disease. It also gives the author's views on aspects of how the field of malaria disease pathogenesis seems to be developing. The hope is to inspire another generation to follow a similarly original course.

Download Full-text

The effect of early resuscitation and ulinastatin on the severe acute pancreatitis in obese patients

Reports of Vinnytsia National Medical University ◽

10.31393/reports-vnmedical-2020-24(3)-13 ◽

2020 ◽

Vol 24 (3) ◽

pp. 449-454

Author(s):

O. Tkachuk ◽

A. Kebkalo

Keyword(s):

Acute Pancreatitis ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Severe Acute Pancreatitis ◽

Interleukin 1 ◽

Obese Patients ◽

Ringer’S Lactate ◽

Bed Days ◽

Experimental Group ◽

Pro Inflammatory Cytokines

Annotation. Obesity is a problem of the third millennium. It is known that obesity is a major factor in the development of various diseases, including acute pancreatitis. Obesity itself is a pro-inflammatory condition with elevated levels of the following pro-inflammatory cytokines: tumor necrosis factor (TNF-a), interleukin (IL) IL-10, IL-6, IL-1b. Acute pancreatitis is also a disease based on the pathogenesis of the cytokine reaction and autolysis. Thus, against the background of the already formed inflammatory response, the inflammatory response intensifies and increases, and the level of pro-inflammatory cytokines reaches critical values. The purpose is to study the effect of ulinastatin on the severe acute pancreatitis in obese patients. To refute or confirm the hypothesis among patients with severe acute pancreatitis and obesity (BMI was 37.48±2.19 kg / m2), two groups were randomized. In the first group (experimental) of 18 patients, a step-up approach was performed. In the second group (control), the total number of which was 18 patients, a standard treatment algorithm was performed. The experimental group suggested the use of early resuscitation with Ringer’s lactate and ulinastatin in the first 5 days of the disease. The drug was administered at a dose of 200,000 IU by intravenous infusion for 1 hour 3 times a day for 5 days. In the control group, resuscitation was performed with 0.9% sodium chloride solution without the use of ulinastatin. Hypothesis was tested by monitoring procalciton and C-reactive protein, interleukin-1 and interleukin-6 over a period of 24 hours, 48 hours, 10 days, 15 days, 30 days, 45 and 60 days. The choice of procalcitonin and CRP was made by calculating the relative risk, as the level of CRP> 200mg / l indicated the preservation of severe disease (RR=2.07; 95% CI=1.65-2.59; p=0.01), and an increase in procalcitonin> 1.8 ng / mg was a predictor of infection (RR=2.27; 95% CI=1.083-4.769; p=0.02). The use of ulinastatin during the first 5 days in the experimental group reduced the level of interleukin-1 from 23.64±4.13 to 8.71±2.49 pg / ml (p=0.001; α=0.05), interleukin- 6 – from 29.72±4.27 to 12.43±2.36 pg / ml (p=0.001; α=0.05). The use of resuscitation with Ringer's lactate solution in combination with ulinastatin for 5 days helped to reduce the level of procalciton in 1.8 times (2.89±0.88 compared with 1.8±0.23 ng / mg; p=0.001; α=0.05). The level of CRP during the period of ulinastatin decreased by 41.68 (267.28±114.11 compared with 225.6±84.9 mg / l; p=0.01; α=0.05). In-hospital mortality was significantly lower in the ulinastatin group (16% vs. 69.6%; p=0.0003; α=0.05). Significantly lower proportion of patients (24% compared to 73.9%; p=0.0005; α=0.05) with multiple organ failure among the study group. Organ dysfunction was acquired on day 5 among patients taking ulinastatin. The length of hospital stay was 49.7±4.2 bed-days, while in the comparison group – 56.67±5.84 bed-days (p=0.01; α=0.05). Thus, the use of Ringer-lactate early resuscitation in combination with ulinastatin has improved the treatment of severe acute pancreatitis in obese patients.

Download Full-text

Combating COVID-19 with Mesenchymal Stem Cell therapy

10.31219/osf.io/3ecda ◽

2020 ◽

Author(s):

Shashikant Ray ◽

Keshav Rajarshi ◽

Aroni Chatterjee

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Therapy ◽

Inflammatory Cytokines ◽

Stem Cell Therapy ◽

Rna Virus ◽

Multiple Organ ◽

Mesenchymal Stem Cell Therapy ◽

Cytokines And Chemokines ◽

Pro Inflammatory Cytokines

The world is currently facing one of its deadliest nightmares, the rise of a global pandemic called COVID-19. The disease is caused by a positive stranded RNA virus called SARS-CoV-2. The virus mainly targets the pulmonary epithelial cells as it’s initial site of infection by letting its surface spike protein interact and bind to the host ACE2 receptor. The internalization and gradual replication of the virus results in an exaggerated immune response triggering release of many pro-inflammatory cytokines and chemokines. This immune storm is responsible for multiple health hazards in the host ultimately leading to multiple organ failure. Mesenchymal stem cell therapy offers a promising approach towards mitigating the delirious effects of the infection in the COVID-19 patients. This therapy has shown to reduce the expression of pro-inflammatory cytokines as well as repair of damaged tissues in COVID-19 patients. This review has been organized to put forward all the positive aruments and implications in support of mesenchymal stem cell therapy as a necessary approach for treating COVID-19 patients.

Download Full-text

Immunomodulation strategies in the critically ill

10.1093/med/9780199600830.003.0312 ◽

2016 ◽

Author(s):

Aline B. Maddux ◽

Gordon R. Bernard

Keyword(s):

Inflammatory Cytokines ◽

Immune Cell ◽

Multiple Organ ◽

Source Of Infection ◽

Immune Paralysis ◽

Mediators Of Inflammation ◽

Delayed Mortality ◽

Anti Inflammatory ◽

Circulating Levels ◽

Pro Inflammatory Cytokines

Severe sepsis is a hyperimmune response to an infectious stimulus resulting in a surge of cytokines and mediators of inflammation. High circulating levels of pro-inflammatory cytokines lead to shock, multiple organ failure, and death in septic patients. It has been recognized that patients with sepsis progress into a state of immune paralysis characterized by immune cell apoptosis and high levels of anti-inflammatory cytokines… Anti-inflammatory cytokines suppress production of pro-inflammatory cytokines and inhibit monocytes from presenting antigens to other immune cells. Immune paralysis probably leads to the patient’s inability to clear infections resulting in the delayed mortality observed in some septic patients. Beneficial therapies for sepsis are limited to the mechanical eradication of the source of infection, antibiotics, the judicious use of fluids to support organ perfusion, and oxygen supplementation. Strategies to counteract the hyper- and hypo-immune phases of sepsis have been tried thus far with only minimal success.

Download Full-text