[Neuroinflammation in the pathogenesis of central neuropathic pain]. / Neirovospalenie v patogeneze neiropaticheskogo bolevogo sindroma.

The problem of chronic pain is a significant question of nowadays medicine due to its high prevalence and treatment ineffectiveness in most cases. It has been proved by means of neuroimaging methods that chronic pain is always associated with glial activation in central nervous system, leading to the disturbance of glial cells participation in the eregulation of neuron microenvironment and neurotransmitter exchange. As a result, interneuronal communication in nociceptive pathways is interrupted and pathological neuroplasticity processes develop, causing the formation of pathological circuits, selfregilated by means of positive feedback. Thus, intervention that is directed to neuroinflammation suppression can by pathogeneticaly approved and effective method to treat chronic pain. In this review basic mechanisms of the inflammation initiation and maintaining in central nervous system in chronic pain are considered, pathological self-regulated circuits with neurons and immune cells are described and current chronic pain medications with antiinflammatiry and antinociceptive properties are listed.

[Biological activity of interferons in the novel coronavirus infection COVID-19].

INTRODUCTION: The immunopathogenesis of the novel coronavirus infection COVID-19 is usually associated with the development of imbalance in the immune response to its causative agent, SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus). This is manifested, in particular, by interferons' (IFNs) deficiency at the beginning of the disease followed by hyperproduction of pro-inflammatory cytokines. The virus causes a decrease in IFN types I (α/ß) and III (λ) levels; changes in IFN type II (γ) are less studied. In this regard, it is relevant to assess the functional bioactive IFN (interferon status) in COVID-19. The aim of the study was to assess the antiviral potential of the body by testing the biologically active IFNs in COVID-19. MATERIAL AND METHODS: We used biological serum samples of COVID-19 patients taken in the acute phase (110 patients on the 1-5 days of the disease) and during rehabilitation (47 patients during 1-3 months after the disease onset). Assessment of interferon status was performed according to the technique developed by the authors and described earlier. RESULTS: The IFN status of patients with COVID-19 in the acute period and in the phase of post-infection rehabilitation was studied вduring the observation period. It was found that SARS-CoV-2 causes a pronounced inhibition of biological activity of IFN types I and II compared to the reference values by more than 20 and 7 times, respectively. During the post-COVID period, incomplete recovery of the IFN system activity was registered, which proceeded very slowly. No cases of reaching physiological indicators of interferon status were identified during the observation period. CONCLUSION: The obtained data on deficiency of the functional biologically active IFN confirm the hypothesis about the predominant role of impaired IFN production of different types in the immunopathogenesis of the novel coronavirus infection.

[Interferon-regulating activity of the CelAgrip drug and its influence on the formation of reactive oxygen species and expression of innate immunity genes in Burkitt's lymphome cells cultures.]

INTRODUCTION: Interferons (IFN) and IFN inducers are effective in suppressing viral reproduction and correcting of the innate immunity mechanisms. The aim of the study was to test the hypothesis of the possible involvement of the IFN inducer CelAgrip (CA) as an activator or suppressor of antiviral effects in Burkitt's lymphoma (LB) cell cultures with different ability to produce Epstein-Barr virus antigens (EBV). MATERIAL AND METHODS: The kinetic analysis of the dynamics of reactive oxygen species (ROS) production and determination of gene group expression by real-time PCR in response to CA treatment were done in human cell lines LB P3HR-1 and Namalva, spontaneously producing and not producing EBV antigens. RESULTS AND DISCUSSION: When treating CA in Namalva cells, a decrease in the ROS activation index was found; in P3HR-1 cells, an increase was observed. After treatment with CA, there was no reliable activation of the IFN-α, IFN-ß and IFN-λ genes in Namalva cells, but the expression of the ISG15 and P53(TP53) genes was increased more than 1200 times and 4.5 times, respectively. When processing the CA of P3HR-1 cells, the expression of IFN-α genes increased by more than 200 times, IFN-λ - 100 times, and the ISG15 gene - 2.2 times. The relationship between IFN-inducing action of CA and the activity of ISG15 and ROS in LB cell cultures producing and not producing EBV antigens is supposed. CONCLUSION: In Namalva cells that do not produce EBV antigens the treatment of CA results in suppression of ROS generation and activation of the expression of genes ISG15 and P53 (TP53); in P3HR-1 cells producing EBV antigens, the opposite picture is observed - the formation of ROS and the expression of the IFN-α and IFN-λ genes are activated and the activity of the ISG15 and P53 (TP53) genes is suppressed.

[Interferon-regulating activity of the celagrip antiviral drug and its influence on formation of reactive oxygen species and expression of innate immunity genes in the follicular lymphoma patients].

INTRODUCTION: Medicines from the group of interferon inducers (IFNs) "swith on" the synthesis of type 1 interferons (IFN-I) and induce the expression of IFN-stimulated genes (ISGs) that regulate innate immunity reactions and protect the host from infectious agents and the tumour pathology.The purpose of the study was to determine the role of the drug celagrip (CA) in the activation of innate immunity genes and the effect on the production of reactive oxygen species (ROS) in patients with follicular lymphoma (FL). OBJECTIVES:  to study the intensity of ROS production and the level of expression of the IFN-α2, IFN-λ1, ISG15, BCL2, P53(TP53) and USP18 genes in response to the treatment of blood cells of patients with FL with the preparation of CA. MATERIAL AND METHODS: The study involved primary cancer patients diagnosed with follicular lymphoma (FL) and healthy volunteers. A kinetic analysis of the dynamics of production of reactive oxygen species (ROS) was performed in whose blood cells, and the expression of the group of genes was determined by real-time PCR in response to CA processing. RESULTS AND DISCUSSION: ROS production by blood cells of patients with FL and volunteers in the presence of CA significantly decreased (P < 0.05). The level of gene expression of ISG15, P53(TR53) and USP 18 in the group of patients with FL was significantly higher than that in the group of volunteers. When treating blood cells with CA, it becomes possible to divide patients with FL into groups with a positive and negative response in accordance with the level of expression of the USP18 gene. We divided FL patients into groups with a positive and negative response in accordance with the level of USP18 gene expression after treatment of blood cells with CA. CONCLUSIONS: The CA drug reduces the production of ROS and simultaneously stimulates the activity of the innate immunity genes ISG15, P53(TP53) and USP18 in the blood cells of patients with FL.

[Cytokine-regulating activity of anti-virus preparation CelAgripus in Burkitt's lymphoma stable B-cell lines.]

INTRODUCTION: Cytokines activated in response to immunosuppressive viral infections can directly or indirectly affect the neoplastic transformation of B cells. In this study, we studied a new substance designed to produce the antiviral drug CelAgrip (CA, CelAgripus), which exhibits interferon (IFN) and cytokine-inducing activity and, apparently, can be used as an activator of antiviral immunity. Purpose - is to evaluate the cytokine-regulating effect of CA in Burkitt's lymphoma (LB) cell lines latently infected with the Epstein-Barr virus (EBV). OBJECTIVES: to study the CA-induced expression of the cytokine genes IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, IFN-α, IFN -γ, IFN-ß, IFN-λ1, IFN-λ2, IFN-λ3, TNF-α in normal and EBV transformed LB cells. MATERIAL AND METHODS: Cell line: the human embryo fibroblasts (HEF), Namalva, Daudi, Raji, P3HR-1. Preparations: CA, gossypol-acetic acid (GAA), sodium carboxymethyl cellulose (Na-CMC). METHODS: RT-PCR and methods for assessing cytotoxicity (MTT and Scepter 2.0 Merck cell counter). RESULTS: The effect of the CA preparation on the expression of IFN-λ, IL-1ß, IL-6, IL-8 and IL-10 genes was revealed. DISCUSSION: We observed the activation of gene expression of IFN-λ, IL-1ß, IL-6, IL-8 and suppression of IL-10 gene activity when treatment CA of LB cells. CONCLUSION: The substance CA has new effects on the activation of the expression of a number of key cytokine genes in stable Burkitt lymphoma cell lines.

[THERAPEUTIC POTENTIAL OF ALPHA-INTERFERON PREPARATIONS DUR- ING SOCIALLY-SIGNIFICANT HUMAN DISEASES OF VIRAL ETIOLOGY].

Interferons (IFN) belong to key cytokines of innate and adaptive immune response and play an important role in anti-viral and anti-tumor protection. At the same time, they possess a pro- nounced immune-modulating, anti-proliferative and anti-fibrotic effect. A general comparative characteristic of human IFN type I (α/ß), IFN type II (γ) and IFN type III (λ) and nosological directionality of contemporary drugs created on their base is examined in the review. Epidemiologic parameters for main socially-significant human diseases of viral etiology are presented: influenza and other ARVIs, herpes infection, chronic viral hepatitis B, C and D. Main attention is given to analysis of effectiveness of therapeutic application of preparations based on IFNα during the in- dicated infections, a specter of main IFNα induced side effects is listed. Recent achievements on the path of creation of principally new drugs based on IFN, that have lower toxicity and higher clinical effectiveness, as well as perspectives of application of preparations based on recombinant IFN for therapy of potentially, dangerous diseases are examined.

[[Antiviral activity of the interferon beta 1a].

The antiviral activity of the interferon beta Ia was studied using the example of the antiviral activity of the drugs interferon beta Ia Genfaxon and Rebif for the influenza and herpes. A pronounced antiviral effect of the drugs against influenza and herpes viruses was-shown far the first time.