RESUMEN
AIMS: To identify an imbalance of cardiac remodeling mediators and monocytes subpopulation in blood, distribution of myocardium macrophages in patients with ischemic cardiomyopathy (ICMP). METHODS: The study engaged 30 patients with ICMP, 26 patients with coronary heart disease (CHD) without ICMP, 15 healthy donors. Concentrations of TGFß, MMP-9, MCP-1, galectin-3 were measured in plasma of blood from the coronary sinus and peripheral blood in CHD patients, as well as in peripheral blood in healthy donors, by enzyme immunoassay method. The ration of classical, intermediate, non-classical, transitional monocytes in peripheral blood of patients and healthy donors was assessed by flow cytometry (expression CD14, CD16); the content of CD68+ macrophages in myocardium - by immunohistochemistry method. RESULTS: In both samples of blood, the content of galectin-3 in patients with ICMP was higher than in CHD patients without ICMP and the level of TGFß was comparable between the groups. At ICMP, the concentration of MMP-9 in sinus blood was higher than that in CHD patients without ICMP in whom an excess of MCP-1 in the general blood flow was determined. The density of distribution of CD68+ cells in the myocardium in patients with ICMP was higher in the perianeurysmal zone than in the right atrium appendage. ICMP was characterized by a deficiency of non-classical monocytes, and CHD without ICMP - by an excess of intermediate cells in peripheral blood. CONCLUSION: Myocardium remodeling at ICMP is mediated by not so much TGFß but intracardiac galectin-3, which determines the subpopulation composition of blood monocytes.
RESUMEN
Proinflammatory cytokines are known to play a crucial role in the pathogenesis of tuberculosis, and gene polymorphisms in the promoter regions of cytokine genes were shown to substantially influence the secretory capacity of immune cells. In the present study, we analyzed the association between polymorphisms of the IL12B, IL18, and IL27 genes and the secretion of the proinflammatory cytokines IL-12Ñ70, IL-18, and IL-27 by myeloid dendritic cells (mDCs) in pulmonary tuberculosis (PTB) patients. The study enrolled 334 patients with newly diagnosed infiltrative and disseminated PTB. Cultivation of mDCs was performed from non-proliferating progenitors of CD14+ blood monocytes. Cytokine secretion was evaluated by measuring cytokine concentration in the mDC culture supernatants using enzyme-linked immunosorbent essay (ELISA). To study cytokine gene polymorphisms, a polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) were performed. Reduced secretion of IL-18 and IL-27 by mDCs in PTB patients was associated with 105A/C polymorphisms of the IL18 gene, and 2905T/G, 4730T/С, and -964A/G of the IL27 gene, respectively. Polymorphism IL12B/insertion had a bidirectional influence on the secretion of IL-12p70, being associated with decreased levels of the cytokine in infiltrative PTB and increased levels in disseminated PTB patients.
Asunto(s)
Citocinas/genética , Células Dendríticas/metabolismo , Interleucinas/metabolismo , Polimorfismo Genético/genética , Tuberculosis Pulmonar/genética , Adulto , Células Cultivadas , Citocinas/metabolismo , Femenino , Humanos , Interleucina-12/metabolismo , Interleucina-18/metabolismo , Masculino , Mycobacterium tuberculosis/genética , Polimorfismo de Nucleótido Simple/genética , Adulto JovenRESUMEN
The study of subpopulation structure of IFNγ-producing T cells in patients with pulmonary tuberculosis revealed a decrease in the number of CD3+ IFNγ+ cells against the background of significantly increased IFNγ secretion in vitro irrespective of the clinical form of the disease and drug sensitivity of M. tuberculosis, most strongly expressed in case of the disseminated tuberculosis. In patients with infiltrative drug-sensitive and drug-resistant pulmonary tuberculosis, increased number of Th1/Th17 lymphocytes (CD4+ IFNγ+IL-17A+) and, conversely, decreased number of blood γδT cells was detected.
Asunto(s)
Linaje de la Célula/inmunología , Interferón gamma/inmunología , Células TH1/inmunología , Células Th17/inmunología , Tuberculosis Resistente a Múltiples Medicamentos/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Antituberculosos/uso terapéutico , Antígenos CD4/genética , Antígenos CD4/inmunología , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Inmunofenotipificación , Interferón gamma/genética , Interleucina-17/genética , Interleucina-17/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , Mycobacterium tuberculosis/patogenicidad , Cultivo Primario de Células , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Células TH1/efectos de los fármacos , Células TH1/microbiología , Células Th17/efectos de los fármacos , Células Th17/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/microbiologíaRESUMEN
We studied possible mechanisms of immunosuppression mediated by regulatory T cells that promotes suppression of antigen-specific immune response to Mycobacterium tuberculosis in patients with pulmonary tuberculosis and eosinophilia. It was shown that the number of CD4(+)CD25(+)Foxp3(+) regulatory T cells with immunosuppressive activity (Treg) increased in the peripheral blood of patients with disseminated destructive forms of pulmonary tuberculosis with multiple resistance of the causative agent to antituberculosis substances and eosinophilia. These changes were accompanied by imbalance in secretion of Treg-associated cytokines (in vitro) manifested in hyperproduction of TGFß and IL-10 and decreased production of IL-2.
Asunto(s)
Eosinofilia/inmunología , Eosinofilia/microbiología , Linfocitos T Reguladores/metabolismo , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Adolescente , Adulto , Linfocitos T CD4-Positivos/metabolismo , Eosinofilia/metabolismo , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/patogenicidad , Factor de Crecimiento Transformador beta/metabolismo , Tuberculosis Pulmonar/metabolismo , Adulto JovenRESUMEN
In patients with infiltrative pulmonary tuberculosis, the increase in IL-6 secretion, the decrease in TGFß production (in case of drug resistance of the causative agent), and unchanged level of IL-1ß secretion by mononuclear leukocytes in vitro were associated with increased number of CD4(+)CD161(+)IL-17A(+) Th17 lymphocytes in the peripheral blood. In patients with disseminated drug-resistant pulmonary tuberculosis, TGFß hyperproduction promoted differentiation of CD4(+)CD25(+)FoxP3(+) Treg lymphocytes with immunosuppressive activity.
Asunto(s)
Diferenciación Celular/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Antígenos CD4/metabolismo , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Masculino , Persona de Mediana Edad , Subfamilia B de Receptores Similares a Lectina de Células NK/metabolismo , Estadísticas no Paramétricas , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo , Factor de Crecimiento Transformador beta/inmunología , Tuberculosis Pulmonar/sangreRESUMEN
Homeostasis of subpopulations Th17- and Treg-lymphocytes plays an important role in a holistic and coordinated process of eradication of pathogens and preventing the spread of infection in the body. Study of molecular mechanisms controlling the balance of these cells in the formation of immune deviation in the pathogenesis of infection are particularly relevant. The article presents the results of a study of mRNA expression of transcription factors Th17- and Treg-lymphocytes--RORC2 and FoxP3, respectively, as well as the presence of these cells in peripheral blood in infectious disease (based on an example of infection caused by Mycobacterium tuberculosis). It was established that during the infiltrative (regardless of drug susceptibility testing) and disseminated drug-susceptible pulmonary tuberculosis accompanied by Th17-polarized differentiation of T-lymphocytes, as evidenced by the increased number of CD4+CD161+IL17A+ cells in the blood in association with increased mRNA expression of the transcription factor RORC2 in lymphocytes. In disseminated drug-resistant pulmonary tuberculosis T-lymphocyte differentiation is carried out mainly in the direction of immunosuppressive Treg-cells, as evidenced by the increase in their number in the blood in association with elevated levels of mRNA expression of the transcription factor FoxP3 in lymphocytes.
Asunto(s)
Factores de Transcripción Forkhead/genética , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , ARN Mensajero/genética , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Tuberculosis Resistente a Múltiples Medicamentos/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Antituberculosos/uso terapéutico , Estudios de Casos y Controles , Diferenciación Celular , Progresión de la Enfermedad , Femenino , Factores de Transcripción Forkhead/inmunología , Regulación de la Expresión Génica/inmunología , Humanos , Inmunidad Innata , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/inmunología , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , ARN Mensajero/inmunología , Linfocitos T Reguladores/microbiología , Linfocitos T Reguladores/patología , Células Th17/microbiología , Células Th17/patología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/patología , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/patologíaRESUMEN
Increased content of CD4(+)CD161(+)IL-17A(+) Th17 lymphocytes in the peripheral blood was found in patients with pulmonary tuberculosis irrespective of the clinical form (infiltrative, disseminated) and variant of the disease (drug-sensitive, drug-resistant). The elevated content of Th17 cells in pulmonary tuberculosis is associated with hypersecretion of Th17-associated cytokines IL-17A and IL-22 in vitro that was most pronounced (in case of IL-17A) in patients with disseminated pulmonary tuberculosis.
Asunto(s)
Interleucina-17/metabolismo , Interleucinas/metabolismo , Mycobacterium tuberculosis/inmunología , Células Th17/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Antígenos CD4/metabolismo , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Subfamilia B de Receptores Similares a Lectina de Células NK/metabolismo , Adulto Joven , Interleucina-22RESUMEN
The analysis of current views on functional and immunoregulatory role of T-lymphocytes-helpers of type 17 (Th17) in anti-infectious immune response is presented, in particular, in the development of protective immune reactions to intracellular pathogens. Particular attention is paid to participation of these lymphocytes and cytokines produced by them in immune response to Mycobacterium tuberculosis invasion. The molecular mechanisms, underlying the predominant development of Th17-lymphocytes and/or regulatory T-cells (Treg), are studied, with evaluation of interconnection of these cell subpopulations in formation of immune imbalance in infectious pathology.
Asunto(s)
Citocinas/inmunología , Inmunidad Innata , Células Th17/inmunología , Tuberculosis/inmunología , Citocinas/biosíntesis , Humanos , Mycobacterium tuberculosis/inmunología , Linfocitos T Reguladores/inmunología , Tuberculosis/microbiología , Tuberculosis/terapiaRESUMEN
The article deals with the characteristics of sup-population composition of T-regulator: cells with suppressor activity and production of immunoregulatory cytokines suppressing immune response (IL-10, TGF-beta) in patients with infiltrative tuberculosis of lungs. It is proved that the leading role in formation of immunodepression and tuberculin anergy under infiltrative tuberculosis of lungs is played by T-regulatory, cells with phenotype CD4+CD25+Foxp3+. It is demonstrated that the immunodepression mediated by cytokine production is connected with increasing of both basal and BCG-induced secretion of IL-10 on the background of decrease of level of production of TGF-beta by mononuclear leukocytes in vitro.
Asunto(s)
Anergia Clonal , Interleucina-10/inmunología , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta/inmunología , Tuberculosis Pulmonar/inmunología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T Reguladores/patología , Tuberculina/administración & dosificación , Tuberculina/inmunología , Tuberculosis Pulmonar/patologíaRESUMEN
Subpopulation structure of regulatory T cells and T helpers of peripheral blood in patients with newly diagnosed pulmonary tuberculosis depending on the clinical form of disease and sensitivity of Mycobacterium tuberculosis to antituberculosis drugs has been analyzed in this work. It has been shown that the leading part in immune suppression at infiltrative, dissemination, and fibrosis-cavity pulmonary tuberculosis is played by natural regulatory CD4(+)CD25(+)Foxp3(+)-T lymphocytes. Thus we estimate increase of their number in blood by drug-resistance and drug-susceptible patients. It has been demonstrated that in patients with fibrocavernous and infiltrative form of the disease and drug-resistant pulmonary tuberculosis the number of CD4(+)CD25(-)Foxp3(+)-regulatory T cells was increasing. In patients with infiltrative pulmonary tuberculosis, including multidrug-resistant M. tuberculosis, an increased number of CD3(+)CD4(+)CD25(-) T helpers is determined by the pathogenic features of the development of the tuberculosis infection and is connected with the activation of Th1-dependent immune response. Reduction in the number of T-helpers in the blood of patients with dissemination and fibrosis-cavity pulmonary tuberculosis mediates inefficient implementation of cell-mediated protective immunity.
RESUMEN
Subpopulation structure of T-regulatory cells and proliferative activity of blood lymphocytes in vitro in patients with different clinical forms of pulmonary tuberculosis were studied in this work. It has been shown that Trn--natural T-regulatory lymphocytes (CD4+CD25+Foxp3+) play a leading role in formation of immune suppression under infiltrative, disseminated and fibrosis-cavernous pulmonary tuberculosis. Besides, their number is increased in blood of both tuberculin-positive and tuberculin-negative patients. Negative correlation between the number of Trn and proliferative activity of blood lymphocytes (basal, mitogen- and antigen-induced)has been established, which testifies about participation of Trn in suppression of lymphocyte proliferation and Th1- and Th2-immune response.
Asunto(s)
Proliferación Celular , Tolerancia Inmunológica , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Tuberculosis Pulmonar/inmunología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/patología , Linfocitos T Reguladores/patología , Células TH1/inmunología , Células TH1/patología , Células Th2/inmunología , Células Th2/patología , Tuberculosis Pulmonar/patologíaRESUMEN
Modern immunological and molecular genetic studies showed that tuberculosis is accompanied by an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes. T allele and homozygous TT genotype of T-330G polymorphism in the IL2 gene, T allele and TT genotype of C-590T polymorphism in the IL4 gene, and CC genotype of A-1188C polymorphism in the IL12B gene are immunogenetic factors that have protective activity against susceptibility to pulmonary tuberculosis. Susceptibility to tuberculous infection is associated with A1A2 genotype of the polymorphic region +3953 A1/A2 in the IL1B gene; G allele and TG and GG genotypes of T-330G polymorphism in the IL2 gene; C allele and CC and CT genotypes of C-590T polymorphism in the IL4 gene; and AC genotype of the polymorphic region A-1188C in the IL12 gene.
Asunto(s)
Alelos , Citocinas/genética , Polimorfismo Genético/genética , Tuberculosis Pulmonar/genética , Adulto , Femenino , Genotipo , Humanos , Interleucina-12/genética , Interleucina-1beta/genética , Interleucina-2/genética , Interleucina-4/genética , MasculinoRESUMEN
The effects of isoniazid and rifampicin on the peripheral mononuclear production of IL-2, IL-12, IL-10, IFN-gamma, and TGF-beta were evaluated in patients with infiltrative pulmonary tuberculosis. Irrespective of the susceptibility of the causative agent to the essential antituberculous drugs, rifampicin was ascertained to initiate increased IL-2 secretion and to reduce the generation of IL-12, IFN-gamma and TGF-beta. Isoniazid suppressed the mononuclear leukocytic production of IFN-gamma in drug-sensitive pulmonary tuberculosis, and conversely, stimulated it in the drug-resistant type. Rifampicin showed a more significant negative effect on mononuclear cytokine-producing activity. In drug-resistant pulmonary tuberculosis, the imbalance of spontaneous, protein- and drug-induced mononuclear secretion of cytokines was established to be more pronounced than in drug-sensitive tuberculosis.
Asunto(s)
Citocinas/metabolismo , Isoniazida/uso terapéutico , Rifampin/uso terapéutico , Tuberculosis Pulmonar/sangre , Adolescente , Adulto , Antituberculosos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto JovenRESUMEN
In article is presented, the analysis of the data of the literature and own researches, concerning molecular-genetic mechanisms of antimycobacterial immunity infringements. The role of the factors defining features of a current and an outcome of a tubercular infection, namely of immunity system condition, feature of infecting microbic Mycobacterium tuberculosis strain biological properties (a genotype, a spectrum of drag sensitivity/resistance), influence of combined antitubercular chemotherapy is disc issed. The opinion is expressed that the given factors are necessary for taking into consideration for working out methodology the personalised preventive maintenance and correction of immunity infringements during pulmonary tuberculosis.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Inmunoterapia , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/inmunología , Tuberculosis/terapia , Antituberculosos/uso terapéutico , Citocinas/biosíntesis , Citocinas/inmunología , Quimioterapia Combinada , Humanos , Inmunidad Celular/genética , Inmunidad Celular/inmunología , Interleucina-12/inmunología , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/genética , Pronóstico , Células TH1/inmunología , Células TH1/metabolismo , Tuberculosis/genética , Tuberculosis/microbiologíaRESUMEN
The relationship between combined injury and sepsis is an important problem of forensic medicine. A total of 227 cases with combined injuries have been investigated postmortem at Bureau of Forensic Medical Expert Evaluations of Moscow in 1997. Sepsis developed in 9.7% cases. The studies revealed a direct cause-and-effect relationship between mechanical injuries and development of sepsis in the overwhelming majority of cases. Sepsis may develop at any period of the traumatic disease, except the first one, and the infection is prone to generalization in the remote postoperative period.
Asunto(s)
Traumatismo Múltiple/patología , Sepsis/patología , Infección de Heridas/patología , Adulto , Distribución por Edad , Anciano , Autopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Moscú/epidemiología , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/mortalidad , Sepsis/etiología , Sepsis/mortalidad , Distribución por Sexo , Infección de Heridas/etiología , Infección de Heridas/mortalidadRESUMEN
Studies of the fractional composition of krill proteins demonstrated that the content of protein fractions changes depending on the time of krill catch. The highest amount of water-soluble proteins is contained by krill caught in December (64%), of salt-soluble by krill caught in June (12%), base-soluble by krill caught in May, September and February (34%). Krill protein contains from 50 to 60% of water- and salt-soluble fractions. Analysis of the amino acid composition of krill proteins showed that it does not differ essentially from that of adequate food proteins.