RESUMEN
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.
Asunto(s)
Linfoma de Burkitt/virología , Herpesvirus Humano 4/genética , Interferón-alfa/genética , Interferón beta/genética , Interferón gamma/genética , Antígenos Virales/genética , Antígenos Virales/inmunología , Antígenos Virales/farmacología , Antivirales/farmacología , Linfoma de Burkitt/genética , Linfoma de Burkitt/inmunología , Citocinas/genética , Regulación de la Expresión Génica/inmunología , Regulación Neoplásica de la Expresión Génica , Herpesvirus Humano 4/patogenicidad , Humanos , Inmunidad Innata/genética , Cinética , Especies Reactivas de Oxígeno/química , Proteína p53 Supresora de Tumor/genética , Ubiquitinas/genéticaRESUMEN
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.
Asunto(s)
Antivirales/administración & dosificación , Citocinas/genética , Linfoma Folicular/tratamiento farmacológico , Proteína p53 Supresora de Tumor/genética , Ubiquitina Tiolesterasa/genética , Ubiquitinas/genética , Adulto , Anciano , Antivirales/efectos adversos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunidad Innata/genética , Interferón-alfa/genética , Interferón gamma/genética , Cinética , Linfoma Folicular/genética , Linfoma Folicular/virología , Masculino , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
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.
Asunto(s)
Linfoma de Burkitt/tratamiento farmacológico , Citocinas/genética , Inmunidad Innata/efectos de los fármacos , Virosis/genética , Antivirales/farmacología , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Linfoma de Burkitt/inmunología , Linfoma de Burkitt/virología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidad , Humanos , Inmunidad Innata/genética , Interferón-alfa/genética , Interferones/genética , Factor de Necrosis Tumoral alfa/genética , Virosis/virologíaRESUMEN
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. Ðnimals 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.
Asunto(s)
Antiinflamatorios/farmacología , Antivirales/farmacología , Herpes Simple/tratamiento farmacológico , Herpesvirus Humano 1/efectos de los fármacos , Queratitis Herpética/tratamiento farmacológico , Queratoconjuntivitis/tratamiento farmacológico , Soluciones Oftálmicas/farmacología , Administración Oftálmica , Animales , Modelos Animales de Enfermedad , Herpes Simple/mortalidad , Herpes Simple/patología , Herpes Simple/virología , Herpesvirus Humano 1/crecimiento & desarrollo , Herpesvirus Humano 1/patogenicidad , Humanos , Queratitis Herpética/mortalidad , Queratitis Herpética/patología , Queratitis Herpética/virología , Queratoconjuntivitis/mortalidad , Queratoconjuntivitis/patología , Queratoconjuntivitis/virología , Masculino , Conejos , Análisis de SupervivenciaRESUMEN
An experimental model of the primary genital herpes (herpes simplex type 2, HSV-2) in the female guinea pigs was suggested to study the infectious process activity of polyprenyl phosphates (PPP) and PPP+acyclovir (AC) complex treatment. The morphofunctional features of the guinea pig ovaries were studied in the control and experimental groups (the latter were inoculated with PPP and/or AC as a primary infection treatment) at the stage of the recurrent genital herpes aggravation. It was shown that in the case of combined PPP +AC use significant changes in the disease symptoms were observed, as well as a decrease in the infectious process activity and duration, and positive remote effect on the ovarian morphophysiology.
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Aciclovir/farmacología , Antivirales/farmacología , Herpes Genital/tratamiento farmacológico , Herpesvirus Humano 2/metabolismo , Fosfatos de Poliisoprenilo/farmacología , Animales , Modelos Animales de Enfermedad , Femenino , Cobayas , Herpes Genital/metabolismo , HumanosRESUMEN
AIM: Study of antiviral activity of moraprenil phosphates (MPP) against herpes simplex type 1 virus (HSV1) in vitro and during experimental infection caused by HSV1 in mice. MATERIALS AND METHODS: Activity of MPP in vitro was tested by the ability to suppress formation of symplasts in VERO cells infected with HSV1, strain VR-3. A series of MPP that suppress virus-induced symplast-formation by 30 times was selected for in vivo experiments. Anti-viral activity of MPP in vivo was studied in HSV-1 infected mice after administration of either prophylaxis or therapy regimens. RESULTS: MPP at the dose of 20 microg/mice during s/c administration exhibited a pronounced prophylactic-therapeutic effect. Effectiveness of MPP during clinically evident herpes against the background of developing neurologic symptoms was demonstrated for the first time. Visual observation of the mice, that had received MPP as the first clinical symptoms of the disease appeared, has shown that against the background of preparation injection the clinical signs have ceased after 2 - 3 days and did not registered at least for the whole duration of the observation period (14 days). CONCLUSION: Active herpes infection is accompanied by the increase of FoxP3 expression in-thymus was shown. Possible mechanisms of anti-viral effect of MPP are discussed.
Asunto(s)
Antivirales/farmacología , Enfermedades Transmisibles/tratamiento farmacológico , Infecciones por Herpesviridae/tratamiento farmacológico , Herpesvirus Humano 1/efectos de los fármacos , Organofosfatos/farmacología , Animales , Chlorocebus aethiops , Infecciones por Herpesviridae/virología , Herpesvirus Humano 1/patogenicidad , Humanos , Ratones , Células Vero , Activación Viral/efectos de los fármacosRESUMEN
Expressed antiviral activity of Fortepren (FP) and Gamapren (GP), polyprenyl phosphate (PPP)-contaning agents, was demonstrated in experiments on mice infected with the human herpes simplex virus, type 1 (HSV1) or the vernal encephalitis virus (VEV). Since both the viral infections are of great social significance, the PPP-containing agents should be considered prospective for the medical practice. The experimental data suggested that both the drugs considerably inhibited the VEV infectiousness in the susceptible cell culture. The quantity of protein E, the main immunogen of VEV, in the culture fluid of the VEV infected cells was shown to be markedly lowered under the effect of FP and GP. It was demonstrated for the first time that FP and GP significantly inhibited evolution of the VEV protein E in the cell culture J-96. The experiments with the infectious rhinotracheitis virus (IRTV) of the corned cattle revealed that FP and GP greatly retarded the HSV1 development in the susceptible cell culture. One of the mechanisms of the antiviral action of the PPP-containing agents was likely the effect on the evolution of the virus proteins in the cells. The impact of FP on production of some key cytokines (CT) was studied on mice with experimental vernal encephalitis (IFN-gamma, IL-4 and IL-12). The content of the above mentioned CT in blood of the mice was determined by the IFA test. Under the normal conditions and in the mice infected with VEV, production of IL-12 and IFN-gamma was shown to be stimulated during the first 3-5 days after the FP administration, whereas in the animals not exposed to FP there was observed stimulation of the IL-4 production during the first 3 days after the contamination, followed by increased production of IL-12 and IFN-gamma.