Tag Archives: cytokines

Immunological mechanisms of increased susceptibility to COVID-19 disease and its severe course in patients with diabetes mellitus type 2 and obesity

K. P. Zak1, M. D. Tronko1, S. V. Komisarenko2*

1V. P. Komisarenko Institute of Endocrinology and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: svk@biochem.kiev.ua

Received: 28 April 2023; Revised: 28 May 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023

In this review, we analyze and summarize literature data and the results of our own research related to the immunity status of patients with type 2 diabetes mellitus (T2D) and those T2D patients who were infected with the SARS-CoV-2 virus. It was shown that in the blood plasma of T2D patients, especially those with ele­vated BMI, the level and ultrastructure of the main cellular components of natural immunity – neutrophils and monocytes – were affected accompanied by high levels of proinflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α). It was suggested that the increased susceptibility of T2D patients to SARS-CoV-2 infection is primarily­ due to a weakening of the innate immune defense against pathogens, whereas in T2D patients who have COVID-19, adaptive T-cell immunity disorders accompanied by a cytokine storm prevail. It was concluded that hyperinflammation in T2D+COVID19 patients is the result of enhancement of already existing before SARS-CoV-2 infection T2D-caused disorders of innate and adaptive immunity, in the mechanism of which cytokines and chemokines play a significant role.

The level pro-inflammatory and anti-inflammatory biomarkers in patients with chronic mechanical low back pain under pulse radiofrequency therapy

I. Tekin1, F. Kosova2*

1Manisa Celal Bayar University Medical Faculty, Department of Anesthesia and Reanimation, Algology, Manisa, Turkey;
2Manisa Celal Bayar University School of Vocational Health Service, Department of Medical Biochemistry, Manisa, Turkey;
*e-mail: fundakosova@gmail.com

Received: 02 June 2022; Revised: 25 July 2022;
Accepted: 29 September 2022; Available on-line: 06 October 2022

Low back pain is a frequent and recurrent condition, often with a non-specific cause. Conventional treatment methods are generally insufficient in the treatment of chronic low back pain. The aim of the study was to estimate the level of IFN, IL-1, IL-6 (proinflammatory), IL-10, IL-4 (anti-inflammatory) and VEGF proteins in the serum of patients with chronic mechanical low back pain under Pulse radiofrequency (PRF) therapy. The study was carried out on 40 patients 20-60 years old, diagnosed with chronic low back pain for at least 4 months, primary complaint on lumbosacral low back pain, pain intensity VAS (visual analog scale) score of 5 and above, not responding well to conservative treatment (analgesic drugs, physiotherapy, etc.). Therapeutic Radiofrequency applications were carried out with an RF generator (RFG 3C Plus, Radionics). Blood samples were taken 1 day before interventional treatment (control), then 1 day (group1) and 15 days (group 2) after. The serum level of IFN, IL-1, IL-6, IL-10, IL-4 and VEGF l was analyzed with ELISA test. It was shown that as a result of PRF treatment the level of IL-1 was decreased while the levels of IL-4 and IL-6 were increased. It was concluded that the increase in serum levels of proinflammatory cytokines may be correlated with the severity of pain and that the increase in the level of anti-inflammatory cytokines reduces pain by reducing inflammation.

Inflammation is the common mechanism of diseases (CMD) in COVID-19 disease during pregnancy and in gestational diabetes mellitus

Sandor G. Vari

Cedars-Sinai Medical Center, International Research and Innovation in Medicine Program, Los Angeles, California, United States

The Regional Cooperation for Health, Science and Technology (RECOOP HST) Consortium, led by Cedars-Sinai Medical Center was formed in 2006, was transformed into an Association in 2012 and includes 17 universities and academic organizations from eight countries: seven in Central and Eastern Europe (Croatia, Czech Republic, Hungary, Poland, Romania, Slovakia, Ukraine) and the United States. RECOOP builds multinational, multidisciplinary collaborations, and assists as well as coordinates the research activities of the sixteen research groups that are the Cedars-Sinai Medical Center – RECOOP Research Centers (CRRCs). https://www.cedars-sinai.org/research/administration/recoop.html.
Implementations of RECOOP’s strategic goals enable diverse talents geared towards integration of new knowledge derived from multiple specialties to investigate Common Mechanism of Diseases (CMD). While some may consider RECOOP’s CMD research strategy unorthodox, recent and timely scientific evidence shows that inflammation is the triggering event in the change of vascularization and it is the common mechanism of these two diseases: COVID-19 Disease during pregnancy and gestational diabetes mellitus (GDM).
Binding of the SARS-CoV-2 virus to the ACE2 receptor and its entrance into endothelial cells plays a role in vascular thrombosis but has a lesser effect placental endothelial dysfunction. The latter is induced by inflammation and exacerbated by proinflammatory cytokines, resulting in ischemic events and creating an upward spiral of an inflammatory reaction in pregnant women, accompanied by similar conditions in the placenta that will ultimately affect fetal development. In mild or moderate COVID-19 disease, changes in placental vascularization and blood flow have similarities to comorbidities in pregnancy such as GDM. However, during severe or critical stages of COVID-19 Disease, the changes could be harsher than those observed in GDM.
In COVID-19 Disease and GDM the immune status of pregnant women and consequently the newborn is altered due to inflammation and characterized by changes in levels of C-reactive protein (CRP), immunoglobulins (IgG, IgM, IgA) and proinflammatory cytokines that are detectable in maternal and umbilical cord blood and in mother milk.
To examine changes and monitor placental angiogenesis it is necessary to measure Vascular Endothelial Growth Factor (VEGF), Placental Growth Factor (PLGF), and Umbilical Cord Blood Sclerostin (UCBS) in maternal and umbilical cord blood serum. The angiogenic activity of sclerostin must be validated with the well-known marker VEGF, which is a proven indicator for changes in vascularization. The morphology of the vascular tree and blood flow in the placenta could be evaluated with three-dimensional power Doppler. The proinflammatory and ischemic effects in the placenta should be quantified with histopathology and immunohistochemistry. Changes in blood flow in the placenta and the morphology of the vascular tree in COVID-19 Disease during pregnancy may have similarities to those observed in GDM.
In summary, to improve maternal and fetal outcomes it is imperative to formulate better strategies for managing pregnancies during COVID-19 Disease and comorbidities like GDM. VEGF, PLGF and UCBS could be predictors of placental weight, birth weight, and fetal outcomes. In addition, further studies are needed to investigate the effects, if any, of proinflammatory and anti-inflammatory cytokines on postnatal development.

Anti-inflammatory and hepatoprotective effects of polyherbal composition in patients with chronic cholecystitis

M. Gahramanova1,2, I. Khalilova3, A. Omarov3,
Ya. Susak4, M. Rudyk2, L. Skivka2*

1Nargiz Medical Center, Baku, Azerbaijan;
2ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine;
3Department of Life Sciences & Center for Cell Pathology Research, Khazar University, Baku, Azerbaijan;
4Bogomolets National Medical University, Kyiv, Ukraine;
*e-mail: realmed@i.com.ua

Received: 21 November 2019; Accepted: 15 May 2020

Herbal preparations are widely used in the complementary treatment of inflammatory diseases including hepatobiliary disorders, among which chronic cholecystitis is one of the most common. This study was aimed to investigate the effect of the water extract from polyherbal composition consisting of eight medicinal plants (Helichrysum arenarium, Mentha piperita, Calendula officinalis, Taraxacum officinale, Polygonum aviculare, Matricaria chamomilla, Portulaca oleracea, Hypericum perforatum) on biochemical and haematologic indices as well as on immune reactivity parameters in patients with chronic cholecystitis. It was found that  consumption of polyherbal tea during 45 days was followed by normalization of liver biochemical indices (serum level of cholesterol, alanine aminotransferase and  aspartate aminotransferase activity, total and unconjugated bilirubin levels and diminution of hematological (leukocytosis, increased erythrocyte sedimentation rate and neutrophil-to-lymphocyte ratio) and immunological (increased serum level of pro-inflammatory cytokines) signs of systemic inflammation in patients with hepatobiliary disorder. The results of the research showed that the studied polygerbal composition can be recommended as a component of the complementary therapy for patients with chronic cholecystitis.

Effect of curcumin on accumulation in mononuclear cells and secretion in incubation medium of Аβ(40) and cytokines under local excess of Аβ(42)-homoaggregates

V. V. Sokolik1, S. M. Shulga2

1SI “Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine”, Kharkiv;
2SI “Institute for Food Biotechnology and Genomics of NAS of Ukraine”, Kyiv;
e-mail:  sokolik67@rambler.ru

The aim of the work was to investigate accumulation of endogenous Aβ40 and cytokines (IL-1β, TNFα, IL-6, IL-10) in mononuclear cells and their secretion into incubation medium under Aβ42-aggregates’ toxicity and anti-inflammatory effects of curcumin. Mononuclear cells were isolated in Ficoll-Urografin density gradient from venous blood of healthy donors, resuspended and used for testing of homoaggregates of Aβ42 (15 nM), curcumin (54 pM) and their combinations on various timescales (0, 1, 2, 3, 6 and 24 hours). Endogenous Aβ40 and cytokines were detected in mononuclear cells and (separately) in incubation medium by ELISA. We demonstrated for the first time that homoaggregates of Aβ42 cause rapid accumulation of endogenous Aβ40 in mononuclear cells and accelerate its secretion into incubation medium. We found increased concentration of TNFα after 3 hours of incubation, and no changes in IL-1β concentration due to secretion of these pro-inflammatory factors into incubation medium. The concentrations of IL-6 in mononuclear cells were increased under effects of Aβ42 homoaggregates, and it was being secreted profoundly into incubation medium. Aβ42 did not affect IL-10 secretion, yet caused an increase in its intracellular concentration after 1 hour of incubation, which was subsequently suppressed. Curcumin prevented the increase in Aβ40 concentration in mononuclear cells and significantly decreased its secretion resulting from Aβ42 toxicity. Curcumin negated the activating effect of Aβ42 on pro-inflammatory cytokines, starting immediately for IL-1β and on 3-6 hours for TNFα, which resulted in decreased extracellular concentrations of these cytokines. The polyphenol also potentiated repleni­shing of intracellular IL-6 and IL-10 concentrations and their secretion into incubation medium.

Effect of β-amyloid peptide 42 on the dynamics of expression and formation of Аβ(40), IL-1β, TNFα, IL-6, IL-10 by peripheral blood mononuclear cells in vitro and its correction by curcumin

V. V. Sokolik1, O. K. Koliada2, S. M. Shulga3

1SI Institute of Neurology, Psychiatry and Narcology, National Academy
of Medical Sciences of Ukraine, Kharkiv;
2SI D. F. Chebotarev Institute of Gerontology, National Academy
of Medical Sciences of Ukraine, Kyiv;
3SI Institute for Food Biotechnology and Genomics, National Academy
of Sciences of Ukraine, Kyiv;
e-mail: sokolik67@rambler.ru

The toxic effect of Аβ-oligomers accompanies chronic inflammation, with cytokines as main mediators. Therefore, the cytokine link of inflammation becomes a new target on the way to restrain amyloidosis. The aim of the study was the effect of aggregated Аβ42 on the dynamics of expression and formation of endogenous Аβ40 and cytokines (IL-1β, TNFα, IL-6, IL-10) by peripheral blood mononuclear cells in vitro and its correction by curcumin. A suspension of mononuclear cells isolated ex tempore using ficoll-urografin gradient from venous blood samples of healthy volunteers were used to study the effects of Аβ42 (15 nM), curcumin (54 pM), and their combined action (at similar concentrations) in time dynamics: 0, 1, 3, 6 and 24 h incubation at 37 °C. Polymerase chain reaction with appropriate primers was used to determine the relative expression of mRNA for AβPP, TNFα, IL-1β, IL-6, IL-10 and enzyme-linked immunosorbent assay – to determine the content of Аβ40 and cytokines in mononuclear suspension during all periods of incubation. The individual dynamics AβPP and cytokine expression was shown under the action of the Aβ42, which had influence on the content of Aβ40, TNFα, IL-1β, IL-6 and IL-10 in mononuclear suspension. Curcumin displayed the inhibitory effect on gene expression of AβPP, TNFα and IL6, which resulted in the decrease of the level of these two cytokines and Aβ40. Thus, the dynamics of anti-inflammatory effect of curcumin in vitro for transcriptional and translational levels of cytokine’s formation by mononuclear cells was shown in the work. Direct inhibitory effect of curcumin on the concentration of endogenous Aβ40 during the 24 h incubation in conditions of toxic action of Aβ42 aggregates was established.

Use of vitamins for correction of the functional state of cytochrome P450 systems at experimental allergic encephalomyelitis

E. P. Pasichna1, G. V. Donchenko1, A. P. Burlaka2, V. S. Nedzvetskiy3,
E. P. Sidorik2, I. I.Ganusevich2, N. V. Delemenchuk1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv;
3Honchar National University, Dnipropetrovsk, Ukraine;
e-mail: ellapasich@gmail.com

It is known that inflammatory cytokines, which level is significantly increased in the pathogenesis of multiple sclerosis (MS), as well as interferon-β, which is used to treat autoimmune diseases, can inhibit cytochrome P450-dependent processes of detoxification and biotransformation. The uncontrolled decrease of the activity of these processes may have a negative affect on the state of patients, so it is urgent to study the functional state of the cytochrome P450 system and to develop effective means for its regulation in these conditions. The effect of vitamin D3 and efficiency of its composition with vitamins B1, B2, B6, PP, E, α-lipoic, α-linolenoic acid and mineral substances (Mg, Zn, Se) in prevention of a functional state changes of cytochrome P450- and b5-dependent systems of the rat brain and liver endoplasmic reticulum at EAE are investigated. It has been shown that the essential decrease of the level of these cytochromes is observed both in the brain and liver. In addition the level of activity of NADH-and NADPH-oxidoreductases, which are part of microsomal electron transport chain components and coupled with monooxigenases, was reduced. These changes confirm the disturbances of a redox state and functional activity of detoxication and biotransformation systems in the studied animal tissues. Supplement of vitamin D3 as well as the composition of biologically active substances, which we developed earlier, effectively eliminated the decrease of the level of cytochromes and activities of NADH-oxidoreductase in immunised rat tissues. Normalization of these disturbances can be explained by antioxidant and membrane-stabilizing properties of applied substances, and also by the ability to reduce the activity of inflammatory reactions by regulation of the level of inflammatory cytokines in rat organism at EAE. Thus the studied vitamin-mineral composition appeared to be more effective to normalize the found disturbances and it can be useful for prevention of exacerbations and for improvement of a status of patients with multiple sclerosis and other diseases, which are accompanied with hyperactivation of immune system.

Laureates of the Palladin Prize of the National Academy of Sciences of Ukraine (2008, 2011)

R. P. Vynogradova, V. M. Danilova

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: valdan@biochem.kiev.ua

In 2008 Z. R. Ulberg, O. V. Karpov and S. V. Veryovka were awarded the Palladin Prize of NAS of Ukraine for the series of scientific works “Colloid-chemical and physical-biochemical aspects of the interaction of nano- and microparticles with cells as a basis for the development of nanobiotechnology ” and in 2011 M. Ya. Spivak, L. M. Lazarenko and N. M. Zholobak received the Prize for the series of works “Molecular and biological characteristics of interferon and creation of scientific approaches to the application of interferon medications and their inducers under pathology“. The article also provides laureates’ biographies.