RESUMO
Cushing's disease is a rare severe neuroendocrine disorder caused by chronic overproduction of adrenocorticotropic hormone by a pituitary tumor. Supraphysiological concentrations of cortisol in endogenous hypercortisolism have an immunosuppressive and anti-inflammatory effect similar to therapy with systemic glucocorticosteroids. This may reduce the activity of the patient's concomitant autoimmune inflammatory diseases. On the other hand, a decrease in cortisol levels during treatment for Cushing's disease may be associated with a reactivation of the immune system that pose a risk of onset or recurrence of an autoimmune disorder. We present our own clinical case demonstrating the development of sarcoidosis after surgical treatment of Cushing's disease.
Assuntos
Doenças Autoimunes , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Sarcoidose , Humanos , Hidrocortisona/uso terapêutico , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/cirurgia , Hormônio Adrenocorticotrópico/uso terapêutico , Sarcoidose/complicações , Sarcoidose/tratamento farmacológicoRESUMO
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.
Assuntos
Diferenciação Celular/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Antígenos CD4/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Subfamília B de Receptores Semelhantes a Lectina de Células NK/metabolismo , Estatísticas não Paramétricas , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Fator de Crescimento Transformador beta/imunologia , Tuberculose Pulmonar/sangueRESUMO
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.
Assuntos
Fatores de Transcrição Forkhead/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , RNA Mensageiro/genética , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , Diferenciação Celular , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Imunidade Inata , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/imunologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , RNA Mensageiro/imunologia , Linfócitos T Reguladores/microbiologia , Linfócitos T Reguladores/patologia , Células Th17/microbiologia , Células Th17/patologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologiaRESUMO
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.