Inflammatory cytokines in pediatric cardiac surgery and variable effect of the hemofiltration process

Perfusion ◽  
2005 ◽  
Vol 20 (5) ◽  
pp. 263-268 ◽  
Author(s):  
Gianluca Brancaccio ◽  
Emmanuel Villa ◽  
Elia Girolami ◽  
Guido Michielon ◽  
Cristiana Feltri ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Interleukin 6 ◽  
Multiorgan Failure ◽  
Interleukin 1 ◽  
Clinical Status ◽  
Anesthesia Induction ◽  
Variable Effect ◽  
Anesthetic Drugs ◽  
Tnf Α ◽  
Interleukin 6 Receptor

Cardiac surgery with cardiopulmonary bypass (CPB) elicits an inflammatory response and has a multitude of biological consequences, ranging from subclinical organ dysfunction to severe multiorgan failure. Pediatric patients are more prone to have a reaction that can jeopardize their outcome. Cytokines are supposed to be important mediators in this response: limiting their circulating levels is, therefore, appealing. We investigated the pattern of cytokine release during pediatric operation for congenital heart anomalies in 20 patients, and the effect of hemofiltration. Tumor necrosis factor a (TNF-α) was elevated after anesthesia induction and showed significant decrease during CPB. Hemofiltration reduced its concentration, but the effect disappeared on the following day. Interleukin-1 (IL-1) increased slowly at the end of CPB and hemofiltration had no effect. Interleukin-6 (IL-6) showed a tendency toward augmentation during rewarming and hemofiltration did not significantly affect the course. Soluble interleukin-6 receptor (sIL-6r) had a pattern similar to TNF-α, but hemofiltration had no effect. On the other hand, interleukin-8 (IL-8) behaved like IL-6. Our findings suggest that baseline clinical status, anesthetic drugs, and maneuvers before incision may elicit a cytokine response, whereas rewarming is a critical phase of CPB. Hemofiltration is effective in removal of TNF-α, but its role is debatable for the control of IL-1, IL-6, sIL-6r and IL-8 levels.

scholarly journals Effect of soluble interleukin-6 receptor α and interleukin-6 secreted by polymorphonuclear leukocytes on tumor necrosis factor-α expression and its production by peripheral blood mononuclear cells

2002 ◽  
Vol 11 (5) ◽  
pp. 325-328 ◽  
Author(s):  
E. Jablonska
Keyword(s):  
Interleukin 6 ◽  
Polymorphonuclear Leukocytes ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Interleukin 6 Receptor ◽  
Factor Α ◽  
Necrosis Factor

Background: It has recently been shown that soluble interleukin-6 receptor (sIL-6R) alone or complexed with interleukin (IL)-6, besides their regulatory role in a wide variety of both normal and abnormal biologic reactions mediated by IL-6, could be an effective stimulator of the cell function.Aims: The key question of the present study is whether the sIL-6Rα or sIL-6R with IL-6 released by polymorphonuclear leukocytes (PMN) can influence cytokine secretion such as tumor necrosis factor-α (TNF-α) by peripheral blood mononuclear cells (PBMC), which together with PMN develop the inflammatory and immune response of a host.Methods: Cells were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 1 h at 37°C in 5% CO2. After incubation, the culture supernatant of PMN was removed and was added to PBMC. The PBMC were cultured for 1 h at 37°C in the same conditions. In the culture supernatants and lysates of PMN, we examined the concentrations of sIL-6R by enzyme-linked immunosorbent assay (ELISA). TNF-α was measured at both protein and mRNA levels. Protein levels were determined by ELISA. To examine TNF-α mRNA expression, we isolated mRNA from PBMC after culture, using TRIZOL Reagent. The quantity of mRNA TNF-α was determined by the Quantikine mRNA assay.Results and conclusion: The results obtained revealed that sIL-6R with IL-6 secreted by PMN may play a regulatory role in the immune response by modulating the TNF-α expression and its production by PBMC. This may have a significant influence on an early phase of the inflammation and other reactions mediated by TNF-α.

scholarly journals Expression of Cytokines and Cytokine Receptors-Genes in Patients with Different Forms of Thyroid Pathology in Ukrainian Population

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Iryna Kamyshna ◽  
Aleksandr Kamyshnyi
Keyword(s):  
Autoimmune Thyroiditis ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
White Blood Cells ◽  
Elevated Serum ◽  
Interleukin 10 ◽  
Thyroid Peroxidase ◽  
Thyroid Peroxidase Antibodies ◽  
Interleukin 6 Receptor ◽  
Peripheral White Blood Cells

Abstract Multiple susceptibility genes can be involved in the development of Hashimoto’s thyroiditis. Some of these genes are implicated in other autoimmune diseases, while others are specific to thyroid autoimmune response. 153 patients with thyroid pathology were enrolled in the study (152 women and 1 man, the average age was 46,02±14,3). They were divided into 3 groups: 16 patients with postoperative hypothyroidism; 65 patients with hypothyroidism resulting from autoimmune thyroiditis, and 72 patients with both AIT and elevated serum an anti-thyroglobulin and anti-thyroid peroxidase antibodies. We used a pathway-specific real-time Polymerase chain reaction array to identify and verify cytokines and receptor pathway-associated gene expression in peripheral white blood cells in randomly selected 12 individuals from each group. In the patients with postoperative hypothyroidism and those with hypothyroidism resulting from autoimmune thyroiditis, the expression of Chemokine (C-X3-C motif) receptor 1, Chemokine (C-X-C motif) receptor 4, Interleukin 6, and Interleukin 6 receptor significantly decreased, while the expression of IL6ST and IL10RA increased. In contrast, mRNA levels of Chemokine (C-X3-C motif) receptor 1, Chemokine (C-X-C motif) receptor 4, Interleukin 6, and Interleukin 6 receptor increased in the autoimmune thyroiditis patients with elevated serum anti-thyroglobulin and anti-thyroid peroxidase antibodies, while the expression of Interleukin 6 signal transducer and Interleukin 10 receptor, alpha decreased in this group of patients. The patients with hypothyroidism resulting from autoimmune thyroiditis and patients with elevated serum anti-thyroglobulin and anti-thyroid peroxidase antibodies had significantly lowered expression of Interleukin 10, while the expression of Interleukin 1, beta and Interleukin 1 receptor, type I was elevated. autoimmune thyroiditis and hypothyroidism affect the mRNA-level expression of cytokines and cytokine receptor genes in a gene-specific manner, and these changes to gene expression can be among the triggers of autoimmune inflammation progression in the thyroid gland. Transcriptional activity of cytokines, inducer, and receptor genes in the peripheral white blood cells can be used as an important minimally invasive prognostic marker of the autoimmune thyroid disease severity.

Aktueller Stand der Therapie der rheumatoiden Arthritis mit biologischen DMARDs

2017 ◽  
Vol 37 (02) ◽  
pp. 120-123 ◽  
Author(s):  
K. Krüger
Keyword(s):  
Interleukin 6 ◽  
Interleukin 1 ◽  
Tnf Α

ZusammenfassungBiologika werden in der Rheumatologie seit 17 Jahren eingesetzt. Sie haben die Behandlungsmöglichkeiten bei Krankheiten wie der rheumatoiden Arthritis (RA) dramatisch verbessert und entscheidend dazu beigetragen, dass heute die Remission bei dieser Erkrankung das Behandlungsziel darstellt. Gegenwärtig sind aus dieser Wirkstoffgruppe neun Substanzen für die Behandlung der RA zugelassen, fünf davon hemmen TNF-α, je eines Interleukin-1, Interleukin-6, B-Lymphozyten und die Aktivierung von T-Lymphozyten. Zusätzlich stehen aktuell drei Infliximab-Bio -similars und ein Etanercept-Biosimilar zur Verfügung. Biologika kommen bei der RA bei Patienten mit ungünstiger Prognose als Zweitlinientherapie (in der Regel im Fall einer nicht ausreichend wirksamen Starttherapie mit Methotrexat = MTX) zum Einsatz, in den übrigen Fällen sollten sie bei Versagen konventioneller DMARDs spätestens als Drittlinientherapie eingesetzt werden. Sie sollten kombiniert mit MTX verwendet werden, so-fern dieser Kombinationspartner zur Verfügung steht. Bei MTX-Kontraindikation oder -Unverträglichkeit sind einige der Substanzen auch für die Monotherapie zugelassen, die beste Wirksamkeit bieten hier Tocilizumab und in zweiter Linie Etanercept. Bei Unwirksamkeit des ersten Biologikums ist ein Switch auf eine andere Substanz aus der Gruppe oft erfolgreich.

scholarly journals Interleukin-6 Blockade With Tocilizumab in Anakinra-Refractory Febrile Infection-Related Epilepsy Syndrome (FIRES)

2020 ◽  
Vol 7 ◽  
pp. 2329048X2097925
Author(s):  
Coral M. Stredny ◽  
Siobhan Case ◽  
Arnold J. Sansevere ◽  
MaryBeth Son ◽  
Lauren Henderson ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
Refractory Status Epilepticus ◽  
Cognitive Outcomes ◽  
Epilepsy Syndrome ◽  
Immune System Dysfunction ◽  
Interleukin 6 Receptor ◽  
Pro Inflammatory Cytokines ◽  
New Onset

Febrile infection-related epilepsy syndrome (FIRES) is characterized by new onset refractory status epilepticus in a previously healthy child that is associated with poor cognitive outcomes and chronic epilepsy. Innate immune system dysfunction is hypothesized to be a key etiologic contributor, with a potential role for immunotherapy blocking pro-inflammatory cytokines, such as interleukin-1β and interleukin-6. We present a case of FIRES refractory to anakinra, an interleukin-1 receptor antagonist, subsequently treated with the ketogenic diet and tocilizumab, an interleukin-6 receptor antagonist, temporally associated with seizure cessation and a favorable 1-year outcome.

scholarly journals Effects of Tocilizumab, an Interleukin-6 Receptor Antagonist, on Cytokine Expression and Animal Survival in a Model of Fatal Acute Respiratory Distress Syndrome

Biomeditsina ◽  
2020 ◽  
Vol 16 (4) ◽  
pp. 60-70
Author(s):  
V. N. Karkischenko ◽  
I. A. Pomytkin ◽  
N. V. Petrova ◽  
S. V. Maksimenko ◽  
M. M. Skripkina ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Interleukin 6 ◽  
Distress Syndrome ◽  
Cytokine Expression ◽  
Animal Survival ◽  
Tnf Α ◽  
Interleukin 6 Receptor ◽  
Receptor Signaling Pathway

This study aims to investigate effects of tocilizumab, a monoclonal antibody to interleukin-6 (IL-6) receptors, on cytokine expression and animal survival in a model of fatal acute respiratory distress syndrome (ARDS) characterized by high mortality rates and increased IL-6 production in the lungs. The expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor (TNF-α) and interferons α (IFN-α) and β (IFN-β) in the lungs was assessed by real-time PCR. Cytokine production was assessed by enzyme immunoassay. Although tocilizumab did not affect the expression of the studied cytokines in the lungs of animals with ARDS, it changed the profiles of their release. An acute multifold increase in the levels of IL-6 in the lungs was observed in the first two hours after the administration of tocilizumab, followed by a decrease of IL-6 to lower values similar to those observed in intact animals. Tocilizumab did not reduce mortality in treated animals with ARDS compared to those without treatment. Thus, the inhibition of the IL-6 receptor signaling pathway alone does not provide an effective solution to the problem of reducing mortality from ARDS associated with the development of a “cytokine storm”.

scholarly journals Immunomodulatory drug therapy for the disease caused by SARS-CoV-2 infection (COVID-19)

2020 ◽  
Vol 48 ◽  
pp. 51-67
Author(s):  
D. E. Karateev ◽  
E. L. Luchikhina
Keyword(s):  
Immunosuppressive Therapy ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
Evidence Base ◽  
Multiple Organ ◽  
Janus Kinase ◽  
High Dose ◽  
Jak Inhibitors ◽  
Interleukin 6 Receptor ◽  
Novel Coronavirus

This systematic review focuses on the state-of-the-art pharmacotherapy of immune disorders in the novel coronavirus infection (COVID-19), leading to a cytokine storm and uncontrolled inflammatory response that causes severe tissue damage and multiple organ failure. A lot of theoretical, experimental and clinical data support the need for immunomodulatory (immunosuppressive) therapy for this disease. It should be emphasized that all immunomodulatory drugs for COVID-19 are prescribed off label, and the evidence base of the results of randomized trials is just being accumulated. We review the immunomodulatory therapy for COVID-19 with the following agents: glucocorticoids, hydroxychloroquine and chloro-quine, type 1 interferons, interleukin-6 antagonists (tocilizumab, sarilumab, olokizumab), interleukin-1 p inhibitor canakinumab, tumour necrosis factor inhibitors (infliximab), Janus kinase (JAK) inhibitors (tofacitinib, baricitinib, ruxolitinib), as well as drugs with other mechanisms of action (abatacept, nivolumab, tacrolimus, sirolimus, fingolimod, melphalan, cyclosporine, methotrexate). At the moment, the most reasonable is the use of interleukin-6 receptor inhibitors, intermediate and high dose glucocorticoids, and JAK inhibitors. Based on the latest data from clinical studies, especially the "Solidarity” trial, the use of hydroxychloroquine and chloroquine seems to have insufficient evidence. There are significant pathophysiological overlaps in the development of immunopathology in COVID-19 and in rheumatic diseases, and the strategy of early aggressive immunosuppressive therapy proposed by a number of researchers almost completely coincides with the current strategies for rheumatoid arthritis.

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