RESUMEN
BACKGROUND: We have shown that mycobacterial antigens and CpG oligodeoxynucleotides downmodulate airway allergic inflammation by mechanisms dependent on T-cell activation. Here, we investigated the participation of the innate response, particularly the role of MyD88 adaptor, and Fas molecules in the effectiveness of DNA-HSP65 or CpG/culture filtrated proteins (CFP) immunotherapy. METHODS: Mice sensitized and challenged with Der p 1 allergen were treated with DNA-HSP65, CpG/CFP, or with adoptively transferred cells from immunized mice. The treatment efficacy was assessed by evaluating eosinophil recruitment, antibody, and cytokine production. RESULTS: In addition to downregulating the Th2 response, DNA-HSP65 and CpG/CFP promoted IL-10 and IFN-γ production. Adoptive transfer of cells from mice immunized with DNA-HSP65 or CpG/CFP to allergic recipients downmodulated the allergic response. Notably, transfer of cells from DNA-HSP65- or CpG/CFP-immunized MyD88(-/-) mice failed to reduce allergy. Additionally, for effective reduction of allergy by cells from CpG/CFP-immunized mice, Fas molecules were required. Although DNA-HSP65 or CpG/CFP immunization stimulated antigen-specific production of IFN-γ and IL-10, the effect of DNA-HSP65 was associated with IL-10 while CpG/CFP was associated with IFN-γ. Moreover, after stimulation with mycobacterial antigens plus Der p 1 allergen, cells from mite-allergic patients with asthma exhibited similar patterns of cytokine production as those found in the lung of treated mice. CONCLUSIONS: This study provides new insights on the mechanisms of allergen-free immunotherapy by showing that both DNA-HSP65 and CpG/CFP downregulated house dust mite-induced allergic airway inflammation via distinct pathways that involve not only induction of mycobacterial-specific adaptive responses but also signaling via MyD88 and Fas molecules.
Asunto(s)
Hipersensibilidad/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Transducción de Señal , Receptor fas/metabolismo , Alérgenos/inmunología , Animales , Antígenos Bacterianos/inmunología , Antígenos Dermatofagoides/inmunología , Proteínas de Artrópodos/inmunología , Asma/genética , Asma/inmunología , Asma/metabolismo , Asma/terapia , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Cisteína Endopeptidasas/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Femenino , Humanos , Hipersensibilidad/genética , Hipersensibilidad/inmunología , Hipersensibilidad/terapia , Inmunoterapia , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Ratones , Ratones Noqueados , Mycobacterium/inmunología , Factor 88 de Diferenciación Mieloide/genética , Oligodesoxirribonucleótidos/administración & dosificación , Pyroglyphidae/inmunología , Bazo/citología , Bazo/inmunología , Bazo/metabolismo , Receptor fas/genéticaRESUMEN
BACKGROUND: The immune response to Mycobacterium tuberculosis is complex and multifactorial, the cytokine system being a major factor in M. tuberculosis immunity. AIM: To analyze the immunohistochemical aspects of tuberculous lymph nodes in immunocompetent patients and search for associations between SOCS and cytokine expression in human tuberculous lymphadenitis. METHODS: Thirteen lymph nodes were assayed by immunohistochemistry for SOCS-1 and 3, STAT-3, RANTES, MIP-1-alpha, ICAM-1, IFN-gamma as well as CD45RO, CD20, CD34, CD68, trypsin and lysozyme. Additionally, the RT in situ PCR was performed for SOCS-1 and 3 mRNA detection. RESULTS: Decreased MIP-1 alpha expression together with reduced SOCS-3 (p=0.042), lysozyme (p=0.024) and CD45RO (p=0.05) was observed in the TB lymph nodes compared to the control lymph nodes. In conclusion, the lymphadenitis due to M. tuberculosis was associated with a downregulation of memory T cells (CD45RO), activated lysozymes and SOCS-3 compared to controls, which may play a role in the long-term bacterial replication and altered immune modulation characteristic of the disease.
Asunto(s)
Citocinas/biosíntesis , Enfermedades Endémicas , Ganglios Linfáticos/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/biosíntesis , Tuberculosis Ganglionar/metabolismo , Adolescente , Adulto , Anciano , Antígenos CD/metabolismo , Citocinas/inmunología , Humanos , Inmunohistoquímica , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Persona de Mediana Edad , Muramidasa/metabolismo , Mycobacterium tuberculosis , ARN Mensajero/inmunología , Proteína 1 Supresora de la Señalización de Citocinas , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/inmunología , Tripsina/metabolismo , Tuberculosis Ganglionar/inmunología , Tuberculosis Ganglionar/patologíaRESUMEN
To determine the prevalence and exposure factors associated with hepatitis B infection in tuberculosis patients with and without HIV type 1 coinfection, the presence of hepatitis B virus serological markers was investigated in a retrospective study. The seroprevalence of hepatitis B virus in patients with tuberculosis only was 14.6%, and in tuberculosis patients coinfected with HIV it increased to 35.8%. In patients with HIV and tuberculosis coinfection, homosexuality constituted the principal exposure factor, while in tuberculosis patients without HIV, a gradual increase in hepatitis B virus seroprevalence was noted along with increasing age. The results demonstrate that hepatitis B infection is highly prevalent in tuberculosis patients in Brazil and suggest that a vaccination program for the general population should be considered in order to prevent further hepatitis B infections.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Hepatitis B/epidemiología , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Brasil/epidemiología , Estudios de Casos y Controles , Comorbilidad , Femenino , Hepatitis B/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , Pruebas Serológicas , Índice de Severidad de la Enfermedad , Distribución por Sexo , Tasa de Supervivencia , Tuberculosis Pulmonar/diagnóstico , Población UrbanaRESUMEN
OBJETIVO. Avaliar a influência no curso clínico e a prevalência de distúrbios hidroeletrolíticos, ácido-básicos e da funçäo renal em pacientes portadores da síndrome da imunodeficiência adquirida (SIDA). Casuística e Métodos. A partir de um protocolo preestabelecido, revisaram-se os prontuários da primeira internaçäo de todos os pacientes admitidos durante o primeiro semestre de 1989. RESULTADOS. Noventa e nove pacientes foram estudados. A prevalência de hiponatremia, no momento da baixa, foi de 45% e durante a internaçäo, de 80,7% dos pacientes avaliados. Hipopotassemia esteve presente em 23,1% dos pacientes e acidose metabólica e insuficiência renal em 20,1 e 28,4%, respectivamente. O risco relativo para mortalidade em pacientes com hipopotassemia foi 4,4. Acidose metabólica e insuficiência renal aguda apresentaram riscos relativos de 12,9 e 21,4. Estes fatores, hipopotassemia (p < 0,01), acidose metabólica (p < 0,001) e insuficiência renal aguda (p < 0,001), estiveram significativamente associados à mortalidade. DISCUSSÄO E CONCLUSOES. Conclui-se que existe uma elevada prevalência das alteraçöes avaliadas nos pacientes com SIDA e que o desenvolvimento de hipopotassemia, acidose metabólica e insuficiência renal aguda está significativamente associado à mortalidade nestes pacientes
Asunto(s)
Humanos , Masculino , Adolescente , Adulto , Persona de Mediana Edad , Acidosis/epidemiología , Lesión Renal Aguda/epidemiología , Hipopotasemia/epidemiología , Hiponatremia/epidemiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Acidosis/complicaciones , Brasil/epidemiología , Factores de Riesgo , Lesión Renal Aguda/complicaciones , Hipopotasemia/complicaciones , Hiponatremia/complicacionesRESUMEN
BACKGROUND: A variety of metabolic and renal disturbances have been described in patients with Acquired Immunodeficiency Syndrome (AIDS) but their influence on the clinical outcome has not been reported. The present study was undertaken in order to evaluate the prevalence of fluid and electrolyte, acid-base, and renal function disturbances in AIDS patients. The influence of these abnormalities on the clinical outcome was studied as well. MATERIAL AND METHODS: Following to a previously established protocol, the charts of all patients hospitalized during the first semester of 1989 were reviewed. RESULTS: The prevalence of hyponatremia was 45% and 80.7% at admission and during hospitalization respectively of 99 patients. Hypokalemia was present in 23.1% of the patients. Metabolic acidosis and renal failure were 20.1% and 28.4% prevalent. The relative risk for mortality in patients with hypokalemia was 4.4. Metabolic acidosis and acute renal failure had relative risks of 12.9 and 21.4. CONCLUSIONS: There is an elevated prevalence of fluid and electrolyte, acid-base and renal function disturbances in these patients. The presence of hypokalemia, metabolic acidosis, and renal failure are significantly associated with mortality in AIDS.