[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.

[Ophthalmic drug films in the therapy of experimental herpetic keratoconjunctivitis.]

INTRODUCTION: The complexity of the treatment of herpetic keratoconjunctivitis is due to the severity of the disease, complications, the transition to chronic relapsing forms and the insufficient effectiveness of the drugs used, which leads to a steady increase in the number of patients. The aim of the study was to evaluate the therapeutic efficacy of the eye drug films «GlazAvir¼ in the experimental model of acute herpetic eye infection in rabbits. RESEARCH OBJECTIVES: to study the specific activity of «GlazAvir¼ and compare the long-term indicators of the level of manifestation of individual clinical signs of keratoconjunctivitis. MATERIAL AND METHODS: In the work we used rabbits of the Chinchilla breed, the herpes simplex virus type 1 and the eye drug films «GlazAvir¼. A model of ophthalmic herpetic infection was formed by infection of rabbits with virus-containing material of a pre-scarified eye cornea against the background of local anesthesia. Аnimals were treated with the drug «GlazAvir¼ - 1 application per day for 7 days. Animals were observed daily for 15 days, then every 3 days until the 25th day of observation. The effectiveness of the drug was evaluated at the peak of the development of the pathological process. RESULTS AND DISCUSSION: There was a decrease in mortality from 50 to 20%, and an increase in average life expectancy by 27.87%, compared with the control in animals treated with «GlazAvir¼. It was noted after activation of herpetic keratoconjunctivitis on the 2nd - 5th day, at the peak of the disease (6-9th day) a statistically significant decrease in the activity of the pathological process (p<0.05) by rabbits treated with the «GlazAvir¼ ophthalmic drug films. The tendency to normalization by the rabbits treated with the «GlazAvir¼ preparation was observed until the 14th day. CONCLUSION: The data obtained indicate the pronounced effectiveness of the «GlazAvir¼ preparation in the treatment of experimental herpesvirus keratoconjunctivitis.

[The effect of Kagocel on herpes virus reproduction]. / Deistvie preparata "Kagotsel" na reproduktsiiu virusa gerpesa.

The effect of an original drug Kagocel on the reproduction of Herpes simplex virus including its mutant strains resistant to basic antiherpetic medicine Acyclovir was evaluated. Kagocel was shown to have a low cytotoxic effect on Vero cell and inhibited reproduction of Herpes virus type 1 and Herpes virus type 2 in noncytotoxic concentrations. Kagocel was also demonstrated to inhibit the reproduction of Herpes virus type 1, resistant to combination of Acyclovir and phosphonoacetic acid. Detection of direct antiherpetic activity of Kagocel in vitro opens good perspectives to its clinical application, especially in combination with Acyclovir, the medication with other antiherpetic mechanism of action.