RESUMEN
Liver cancer is a highly lethal cancer, in which local tumor microenvironment and systemic immune suppression allow tumor to escape immune surveillance. Intervening in tumor microenvironment by locoregional treatment options can be beneficial for patients. We aimed to study changes in serum cytokines levels due to local disturbance of tumor microenvironment after radiofrequency thermal ablation procedure compare to liver resection in patients with primary and metastatic liver cancer. A total of 17 patients with primary (HCC and Cholangiocarcinoma) and secondary (metastatic) liver cancer were enrolled in this prospective study. Out of 17 patients, 7 were referred to RFA procedure and another 10 underwent surgical liver resection using non-RF based devices. Blood samples were collected from each patient before and after 1 and 3 months of treatment. The following serum cytokines: IL-10, IL-17, INF-γ, TGF-ß were assayed by ELISA (ebiosciences, USA). RFA procedure unlike liver resection decreased serum level of IL-10 in patients with liver cancer. No significant changes in the level of the studied cytokines were revealed.
Asunto(s)
Carcinoma Hepatocelular , Ablación por Catéter , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirugía , Citocinas , Humanos , Neoplasias Hepáticas/cirugía , Estudios Prospectivos , Microambiente TumoralRESUMEN
The aim of our study is to evaluate the mechanisms of anti-inflammatory property of Tagetes patula L. (French Marigold) flower extracts and its protective effect on renal epithelium against uropathogenic E. coli infection. Thus, in this study, a number of in vitro assays were performed to evaluate the antioxidant and anti-inflammatory activities of Tagetes patula L flower extract (water soluble part of French Marigold flower, extracted with chloroform). MTT assay was performed to determine the effect of French Marigold flower extract on cell viability in MDCK cells activated with 100ng/mL of LPS. We investigated the effect of Tagetes patula L. extract on LPS-stimulated levels of NO and TNF-α production by Griess reaction based colorimetric assay and ELISA respectively. Also, we analyzed content of the French Marigold flower extract by HPLC. Our results demonstrated that TPE protected MDCK cells and increased their viability. Also, TPE had a strong inhibitory effect on NO secretion. These effects were due to inhibition of TNF-α induced pro-apoptotic pathway. The Tagetes patula L extract represents a rich source of lutein and its antioxidant property can be caused by lutein. Our results suggest that TPE could be developed as an anti-oxidant and anti-inflammatory agent derived from natural products.
Asunto(s)
Infecciones por Escherichia coli , Riñón , Extractos Vegetales , Tagetes , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Flores , Humanos , Inflamación/tratamiento farmacológico , Riñón/efectos de los fármacos , Riñón/microbiología , Extractos Vegetales/farmacología , Tagetes/químicaRESUMEN
Hepatocellular carcinoma (HCC) is a highly lethal and the most common primary liver cancer with increasing worldwide incidence. Pathogenesis of HCC is immune mediated, however, not completely understood. Chronic low-grade inflammation alters both innate and adaptive immune responses. As a result tolerogenic environment is established in damaged organ. Up to date, incomplete understanding of HCC pathogenesis and the extend of biomarker variability among patients represent the major obstacle for early diagnosis and for the choice of effective treatment. Among current treatment options for HCC, thermal ablation strategy, which in addition to cancer eradication provides adjuvant/"danger"signal to the patient's immune cells, has demonstrated its active immunotherapeutic effect. In ongoing phase I/II clinical trials, tumor antigen loaded dendritic cell (DC)-based vaccines as well as tumor-specific cytotoxic T cells are being tested. Genetically redirected T cell therapy and more refined autologous vaccines are still awaiting approaches in HCC. The topic of this review focuses on current and bench-to-bedside immunotherapeutic strategies for HCC and discusses their advantages and limitations in clinic. We also weight up several prospective immunotherapeutic approaches which in theory have the potential for further implication in HCC. Combination of the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression ought to be a key objective in these future developments.
Asunto(s)
Carcinoma Hepatocelular/terapia , Inmunidad Innata , Inmunoterapia , Neoplasias Hepáticas/terapia , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/uso terapéutico , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Humanos , Tolerancia Inmunológica , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Aging is accompanied by a loss of homeostasis, which leads to increase of susceptibility and vulnerability to cancers, cardiovascular, neurodegenerative and autoimmune diseases. Numerous studies have been suggested that even in the absence of acute infection ageing associated with chronic low-grade inflammation and the underlying cause of this process may be an immunosenescence as well as shifts production of cytokines levels. However, the results on age-related alterations of these cytokine levels are inconsistent. The main aim of our study was to evaluate how the pro- and anti-inflammatory cytokines and lipoproteins fraction varies through aging as well as how these changes related each other in an apparently healthy population. For this purposes, 220 healthy volunteers were selected on the basis of clinical records and laboratory examinations. Individuals with various health problems were excluded. Fasting triglycerids (TG), low and high density lipoproteins (LDL and HDL) and cytokines (IL-6, IL4, 10, 17, IFN, TNF) levels were measured using commercial assay kits. The statistical analysis was performed using SPSS (Chicago, IL, USA). The results revealed that all studied cytokines levels did not fluctuate by gender. LDL means value differ significantly between men and women. Age are not main predictor for HDL, TG, IL4, IL6, IFN circulating levels, however, the production of LDL, IL17 and IL10 showed significant deviations through aging: especially, LDL and IL17 were augmented, while IL-10 were reduced. It is interestingly, that besides the age, LDL levels were correlated with TNF-alfa and IL10, while triglyceride were only associated with IL10 levels. It has to be note that the correlations did not changes after adjustment of age. The result of our study shown that lipoproteins (LDL, TG) and cytokines (TNF, IL10, IL17) levels are linked and can be used as a prognostic markers of cardiovascular diseases development.
Asunto(s)
Envejecimiento/sangre , Inflamación/sangre , Lípidos/sangre , Triglicéridos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Colesterol/sangre , Dislipidemias/sangre , Dislipidemias/patología , Femenino , Voluntarios Sanos , Humanos , Inflamación/patología , Lipoproteínas/sangre , Lipoproteínas/fisiología , Masculino , Persona de Mediana EdadRESUMEN
Some changes in lipid metabolism and immune status occurring at aging are accompanied with development of inflammatory metabolic disorders and age-associated pathologies. It is well-known that permanent stimulation of immune responses may lead to hyperlipidemia that, in its turn, may evoke immune disturbances and affect the auto-inflammation processes. It seems important to explore a mutual relationship between lipid metabolites and immunology markers in order to better manage the age-associated diseases. In Georgian population the study on associations between the lipid metabolism and the immunological parameters might be especially interesting due the specific geo-climate environment and dietary peculiarities of the country. Study involved 250 healthy volunteers at the age of 18-80 years that were tested on the lymphocyte sub-populations (CD3+CD4+, CD3+CD8+, CD4+CD8+, CD4+CD25+FoxP3+) in peripheral blood, as well as on the levels of lipids (Low-and High density lipoproteins, triglycerides and total cholesterol levels. The study revealed statistically significant differences between the under-60 and above-60 age groups by the level of lipids (low density lipoproteins and total cholesterol) and of CD4+CD25+FoxP3+ cell counts in the healthy population of Georgia. Meanwhile, the lipid fractions (low density lipoproteins, triglycerides and total cholesterol) showed statistically reliable positive correlation with CD4+CD8+ cell but negative correlation with CD4+CD25+FoxP3+cell counts.
Asunto(s)
Envejecimiento/sangre , Citocinas/sangre , Inflamación/sangre , Lípidos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Colesterol/sangre , Femenino , Voluntarios Sanos , Humanos , Inflamación/patología , Lipoproteínas/sangre , Lipoproteínas/fisiología , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
Type 1 diabetes (T1D) is an inflammatory disease of the pancreatic islet, in which insulin-producing ß-cells are preferentially destroyed to varying degrees by the concerted action of autoreactive T-cells and monocytic cells. Th1-type cytokines (IL-2 and IFN-γ) correlate with T1D, whereas Th2 (IL-4 and IL-10), Th3 (TGF-ß), and T regulatory cell-type cytokines (IL-10 and TGF-ß) correlate with protection from T1D. An altered balance between the proinflammatory and regulatory T-cell responses, in which T regulatory cells lose the battle, leads to T1D. The aim of current study was to determine the role of CD4+CD25+ regulatory T cells and cytokines: IFN-γ, IL-6, TNF-α, IL-10, IL-4, IL-17 in pathogenesis of T1D.The study was carried out on 71 patients suffering from T1D at the department of endocrinology, Tbilisi State Medical University and Diabetic Children Association. The circulating levels of (IFN-γ, IL-6, TNF-α, IL-10, IL-4, IL-17) were determined by ELISA according manufactures' protocol (R&D Systems Inc., USA). Tregs - CD4+CD25+ frequency was determined on cytofluorometer (BD FACSCalibur flow cytometer, USA). Statistical analysis was performed by using STATISTICA 8.0 for PC (Statsoft Inc., Minneapolis, USA) and Mann-Whitney U-test. Our study revealed significant decrease of IL-6, TNF-α, IL-10 and IL-4 plasma levels (1.197-, 1.188-, 1.504- and 1.840-times respectively) and increase of IL-17 plasma level (2.311-times) on the background of almost unchanged frequency of Tregs in patients with type 1 diabetes. In T1D patients CD4+CD25+ Tregs frequency did not correlate with diabetes duration and positivly correlated with age and IL-4. We supposed that decreased level of IL-4 and IL-10 reflects inhibited functional activity of these cells. We suggested that shifted balance of Th17/Tregs towards inflammatory IL-17 producing cells and decreased levels of suppressive cytokines IL-4 and IL-10 play crucial role in T1D. Future studies are needed to clarify changes in which subsets of heterogenous population of regulatory cells are associated with diabetes duration and how the therapy affects their frequency and function.
Asunto(s)
Citocinas/sangre , Diabetes Mellitus Tipo 1/inmunología , Inmunidad Celular , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Diabetes Mellitus Tipo 1/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Nitric oxide (NO) is a free radical involved in the regulation of many physiological processes. NO exerts important effects on liver in health and diseases. In the present study, we attempted to evaluate the influence of plaferon LB on the liver injury in two experimental models: immune-mediated and mechanical (traumatic shock) liver damage models. The results of our study demonstrated that plaferon LB decreased levels of NO in traumatic shock, but enhanced NO expression on con-A induced hepatitis. Furthermore, plaferon LB inhibited development of metabolic changes in liver tissue and facilitated restoration of hepatocyte function and structure of the tissue. Thus, our data revealed that plaferon LB was a powerful regulator of NO levels in experimental liver injury. Further investigations are needed to determine pro- and anti-apoptotic properties of plaferon LB in the liver.
Asunto(s)
Neuropéptidos/farmacología , Choque Traumático/tratamiento farmacológico , Animales , Hipoxia Encefálica/etiología , Hipoxia Encefálica/prevención & control , Hígado/lesiones , Hígado/metabolismo , Ratones , Óxido Nítrico/metabolismo , Ratas , Choque Traumático/complicaciones , Heridas y Lesiones/tratamiento farmacológicoRESUMEN
The proliferation activity of monolayer culture of Madin Darby Canine Kidney (MDSK) cells is suppressed by a thermostable protein factor of renal tissue of white rats and of humans. Under the influence of renal factors (RF), a decrease in cell number, and suppression of DNA synthesis and mitotic activity in MDCK cells occur. The inhibition of proliferative activity of cultured cells under the influence of RF was substantiated also by MTT assay. It was established that the inhibitory influence of RF is stipulated by suppression of RNA synthesis. It follows that RF may inhibit division of MDCK cells via suppression of gene expression in G1-phase. Similar factors were obtained from renal cells of different systematic groups of organisms (snail, frog, fish, pigeon, guinea pig, swine).
Asunto(s)
Factores Biológicos/farmacología , Epitelio/efectos de los fármacos , Riñón/metabolismo , Animales , Factores Biológicos/aislamiento & purificación , Línea Celular/fisiología , Proliferación Celular/efectos de los fármacos , ADN/biosíntesis , Perros , Regulación hacia Abajo , Epitelio/fisiología , Humanos , Mitosis , TemperaturaRESUMEN
It was demonstrated in in vivo and in vitro experiments that interleukin-2, obtained by cultivation of donor lymphocytes and purified by gel filtration, induces the production of mouse and human killer lymphocytes possessing high cytolytic activity against tumor cells. Interleukin-2 does not cause irreversible changes of the physiological and morphologic indices of vital activity in mice.
Asunto(s)
Antineoplásicos , Interleucina-2/uso terapéutico , Animales , Pruebas Inmunológicas de Citotoxicidad/métodos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Interleucina-2/aislamiento & purificación , Interleucina-2/farmacología , Interleucina-2/toxicidad , Células Asesinas Activadas por Linfocinas/efectos de los fármacos , Células Asesinas Activadas por Linfocinas/inmunología , Leucemia P388/tratamiento farmacológico , Leucemia P388/inmunología , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos DBA , Factores de Tiempo , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/inmunologíaRESUMEN
Specific cytolytic and natural killer activity of peripheral blood lymphocytes was studied in 12 patients with metastatic melanoma. The cytolytic activity of lymphocytes against autologous tumor cells was found in 8 patients. It appeared significantly enhanced by pretreatment of tumor target cells with concanavalin A (Con A). The natural killer activity in all the patients was 2-10 times as high as the specific cytolytic activity. Stimulation of patient lymphocytes with autologous tumor cells or with the mixture of lymphocytes from 5 allogeneic donors induced the generation of highly active T killers possessing natural killer and specific antitumor cytolytic activity.
Asunto(s)
Melanoma/inmunología , Linfocitos T Citotóxicos/inmunología , Adulto , Células Cultivadas , Pruebas Inmunológicas de Citotoxicidad , Femenino , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Activación de Linfocitos/efectos de los fármacos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Melanoma/secundario , Persona de Mediana Edad , Linfocitos T Citotóxicos/efectos de los fármacosRESUMEN
Interleukin-2 (IL-2) was isolated from donor peripheral blood lymphocytes and from JURKAT T-lymphoma cells. The purification procedure including gel filtration on DEAE and CM-Sephadex resulted in a 400-fold increase of the enzyme specific activity. It was shown that optimal proliferation of T-lymphocytes occurs upon consecutive treatment of cells with phytohaemagglutinin and IL-2 as well as in the presence of a serum. The properties and procedure of isolation of the long proliferating line of IL-2-dependent T-cells B-5 were described. Proliferation of B-5 cells completely depended on the presence of IL-2 in the medium, although long-term proliferation occurred upon periodic stimulation of cells with the antigen (allogenic lymphocytes). In the absence of IL-2 B-5 cells decay within 36 hours. The perspective uses of IL-2 prepared from the cultural fluid of human peripheral blood lymphocytes for adoptive immunotherapy of tumours and the applicability of IL-2-dependent B-5 cells for testing the activity of IL-2 preparations from various sources are discussed.