Expression of progesterone-induced blocking factor in severe preeclampsia and its association with immune tolerance imbalance / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore progesterone-induced blocking factor (PIBF) expression in the placenta and blood of patients with severe preeclampsia and its relationship with immune tolerance imbalance.</p><p><b>METHODS</b>Forty-seven patients admitted between January and December, 2012 were enrolled in this study, including 25 patients with early-onset severe preeclampsia (EOPE) and 22 with late-onset severe preeclampsia (LOPE), with 25 women with normal pregnancy serving as control group. The antenatal blood and postpartum placenta were collected for immunohistochemical staining to detect PIBF expression in the placenta and for testing serum PIBF level using ELISA. Flow cytometry was used to detect the percentage of circulating Th1 and Th2 cells and the Th1/Th2 ratio was calculated.</p><p><b>RESULTS</b>PIBF was expressed in decidual cells, syncytiotrophoblasts and partial cytotrophablasts. The serum PIBF levels were 213.58 ± 44.93 ng/ml in EOPE group, 243.00∓61.19 ng/ml in LOPE group and 273.91 ± 48.57 ng/ml in control group. There were significant differences in serum PIBF, blood Th1/Th2 and placenta PIBF-IOD among the 3 groups (P<0.05). EOPE group had significantly lower serum PIBF, lower llacental PIBF quantity (PIBF-IOD) and higher blood Th1/Th2 than the control group (P<0.05). Serum PIBF in women with severe preeclampsia was positively correlated with placenta PIBF-IOD and negatively with blood Th1/Th2 ratio (P<0.05), but a negative correlation between serum PIBF and 24-hour urinary protein was found only in EOPE group (P<0.05).</p><p><b>CONCLUSION</b>The immune tolerance imbalance mediated by PIBF may participate in the pathogenesis of severe preeclampsia. PIBF, the immune suppressor secreted by lymphocytes of pregnancy women, is also a protective factor against severe preeclampsia, which is expected to be a new target in therapy.</p>

Role of IL-10 in immune suppression in cervical cancer.

Cervical cancer is the second most common cancer in the women worldwide and the most frequent in developing countries, including India. Human papilloma virus (HPV) is the major etiological factor in cervical cancer patients. Host factors are also critical in regulating tumor growth and cytokines that modulate immunologic control may be of particular importance. In the present study, we investigated the correlation between the presence of HPV and type of cytokines expressed in cervical carcinomas and attempted to elucidate the possible reasons for the immune suppression. Cytokines investigated were type-1 cytokine IFN-gamma (shows immunostimulatory function and capable of limiting tumor growth) and type-2 cytokines IL-4, IL-10 and IL-6 (show immunosuppressive function and capable of stimulating tumor growth). Our data demonstrated the presence of HPV sub-types 16 and 18 in 86% and 13.8% of cervical tumor biopsies, respectively. The cervical tumor biopsies showed increased presence for mRNA for IL-10 and IL-1alpha, while none of the biopsies showed expression for IFN-gamma. A correlation was observed between the presence of HPV in cervical tumor biopsies and mRNA for IL-10. Increased percentages of CD4+CD25+ regulatory T cells (Tregs) were observed in circulation in cervical cancer patients, providing evidence for increased immune suppression. IL-10 may play a key role in maintenance of Tregs and explains the immunosuppressive state of cervical cancer patients.

Detección de títulos de anticuerpos contra anemia infecciosa aviar y su relación con otros virus inmunosupresores en pollos de engorde: estado Zulia Venezuela / Detection of chicken infectious Anemia antibodies and their relationship with other immunosuppressor virus in broilers chicken: Zulia state Venezuela

En Venezuela, la incidencia de enfermedades respiratorias virales e inmunosupresoras son dos de los mayores problemas en la industria avícola nacional, y hasta el momento no se cuenta con suficiente información epidemiológica al respecto que ayude a establecer medidas de control, por lo que el objetivo de esta investigación fue determinar serológicamente la presencia de anemia infecciosa aviar, reovirus y gumboro, y su relación entre ellas, así como determinar el nivel de anemia en las aves evaluadas. Se tomaron muestras de aproximadamente 14 a 15 aves, de forma semanal a diferentes edades (1, 7, 14, 21, 28, 35 y 42 días), en tres granjas comerciales, tomándose un total de 295 aves. Los títulos de anticuerpos se midieron a través de la prueba ELISA, y el nivel de anemia, por la técnica de microhematocrito. Se detectaron porcentajes de anticuerpos séricos: 90,8 por ciento (268/295) para anemia infecciosa aviar; 82,4 por ciento (244/295) para reovirus y 97 por ciento (286/295) para la enfermedad infecciosa de la bursa. En cuanto a los valores de hematocrito se encontró en forma general que, el 19,6 por ciento (58/295) de las aves evaluadas presentaron anemia, mostrando valores de hematocrito entre 20 y 27 por ciento. Se observó una correlación positiva altamente significativa entre la anemia infecciosa aviar y los otros virus inmunosupresores estudiados, con gumboro (r=0,437; P<0,0001) y reovirus (r=0,312; P<0,0001). Los resultados obtenidos en este trabajo permiten demostrar la presencia del virus de la anemia infecciosa aviar en pollos de engorde en la región, de manera aislada o asociada con reovirus y gumboro, que pudiesen estar afectando en forma subclínica o clínica las granjas avícolas zulianas.

The incidence of viral respiratory and immunosuppressant diseases are two of the biggest problems in the Venezuelan poultry industry, however in the country, there is not enough epidemiological information that helps to establish control measures. The aim of this research was to determine the presence of serological chicken anemia virus, reovirus and gumboro, and it´s correlation between them as well as to determine the level of anemia in the evaluated birds. In this research, approximately fourteen or fifteen (14 or 15) birds were tested weekly and at different ages (1; 7; 14; 21; 28; 35 y 42 days), in three commercial farms. The samples were taken from a total of 295 birds. The viral antibodies were determined by ELISA test and the anemia levels by micro-hematocrit. The presence of seropositivity was 90.8% (268/295) for the chicken anemia virus, 82.4% (244/295) for reovirus and 97% (286/295) for gumboro. Of the total, 9.6% (58/295) of the evaluated birds presented anemia, showing values of hematocrits between 20% and 27%. A positive correlation was found between chicken anemia virus and the other immunosuppressor viruses studied, gumboro (r=0.437; P<0.0001) and reovirus (r=0.312; P<0.0001). The obtained results in this research demonstrated the presence of viral anemia, in broilers, in the Zulia Region, with or without the presence of reovirus and/or gumboro. That could have an effect, in either sub-clinical or clinical forms.

Papel inmunológico de la progesterona en el mantenimiento del embarazo / Immunological role of progesterone in the maintenance of pregnancy

Progesterone is an essential hormone for pregnancy maintenance. This hormone acts by binding to its intracellular receptor or by rapid non-genomic actions to regulate a wide variety of biological functions in the feto-placental unit. Progesterone regulates blastocyst implantation and placental development by inducing immunosupression through type Th2 cytokines secretion. This review summarizes current research about the role of progesterone as critical regulator of expression and secretion of cytokines by T-cell and other placental cells.

La progesterona es una hormona esteroide muy versátil y esencial para el mantenimiento del embarazo. El principal mecanismo de acción de la progesterona es el clásico, vía receptor intracelular, regulando diversas funciones, aspectos celulares y vías moleculares implicadas en el proceso de la implantación. Asimismo existen mecanismos adicionales que no dependen de la interacción del complejo hormona receptor con la maquinaria transcripcional y que son capaces de regular rápidamente cascadas de señalización que determinarán la respuesta de la célula. En particular se ha demostrado que la progesterona ejerce efectos inmunosupresores durante la gestación al favorecer la secreción de citocinas de tipo Th2 por los linfocitos T, evento importante para regular el sistema inmunológico materno y evitar el rechazo de la placenta. El objetivo de esta revisión se centra en analizar la influencia de la progesterona en la interfase materno-fetal sobre la expresión y secreción de citocinas por las células T y no T como es el caso del trofoblasto.

A preliminary study on the immune suppressive protein of stress in human tonsil / 生理学报

Our previous work demonstrated that under the conditions of restraint stress and under the control of central nervous system (CNS), an immune suppressive protein of stress (ISPS) was generated in peripheral lymph tissue and released into the blood stream, acting as an immune suppressor. In the present work, a protein similar to ISPS was found in human tonsil (a peripheral lymph tissue). Human tonsil was homogenized and the extract was prepared. It was found that lymphocyte proliferation was significantly suppressed by the extract. The suppression induced by the extract was partially reversed by the monoclonal antibody against ISPS (2C4). In ELISA test, the extract was able to bind to the monoclonal antibody. By immunohistochemistry, many ISPS positive cells were found in human tonsil. The ISPS positive cells were also found in human lymph nodes. Taken together, all the results demonstrate that a protein similar to ISPS may exist in human peripheral lymphoid tissue.

Immunotherapy for visceral leishmaniasis: ability of factors produced during anti-leishmania responses of skin test positive adults to inhibit peripheral blood mononuclear cell activities associated with visceral leishmaniasis

The course of human Leishmania chagasi infections appears to be determined by the balance between type 1 (T1) CD4+ and CD8+ suppressor (Ts) cell activities. Skin test positive adults living in hyperendemic areas who have no history of visceral leishmaniasis (VL) have T1 CD4+ T cell immunodominant responses against L. chagasi. The cytokines they secrete during anti-leishmania responses are a problable source of cytokines which inhibit the CD8+ Ts cells associated with VL. The ability of supernatants generated from peripheral blood mononuclear cells derived from skin test positive adults to reverse immune responses which appear to be mediated by CD8+ Ts cells was assessed in three sets of screening assays. The supernatants displayed three candidate factors. One, which could be explained by Leishmania antigens in the supernatants, decreased high endogenous IL-10 secretion characteristic of one class of VL patients. A second activity decreased high endogenous proliferation characteristic of the same class of patients without decreasing antigen specific proliferation. The third activity inhibited or killed CD8+ T cells but not CD4+ T cells. These activities might be useful in treating VL.

Immune suppressive drug in the renal disease

The nature of immunoresponse is to protect of body from antigens, but excessive immunoresponse leads harmful and serious effects for body. The communosuppressive drugs were effective in the treatment of patients with renal transplantation, primary nephritic syndrome and pyelonephritis. However, the drugs cause many side and adverse effects such as infection. It should monitor clinical manifestations and examine periodical blood during the treatment to reduce the dose or interruption of the treatment.

Suppressor activity in Leishmania donovani-infected hamster serum: reversion by delipidated bovine serum albumin and role in cell cycle events

Visceral leishmaniasis caused by Leishmania donovani, is a chroníc disease with a high mortality rate. This protozoan induces a serious dysfunction of the immune system characterized by suppression of the cellular response to parasite antigens. We provide evidence for the involvement of lipids in the immunological alterations of experimental leishmaniasis. Sera obtained from 60-day-infected hamsters present increased triglyceride levels. Inhibition of cell proliferation was observed when splenocytes from normal hamsters were stimulated with concanavalin A in the presence of 3 per cent infected hamster serum (IHS) (Control 50 + 3 (x 10(3)) Cpm; IHS 5 ñ 1 (X 10(3)) cpm). This inhibition was reversed by the addition of 5 mg/ml of delipidated bovine serum albumin (BSA) to the cultures (Control 65 ñ 1 (X 10(3)) cpm; IHS 75 ñ 3 (x 10(3)) cpm). The inhibitory effect of IHS was demonstrable only when added to the culture simultaneously with the mitogen. This effect was not as intense on fresh, pre-activated cells or on the CTLL-2 cells. This cell line stimulated by IL-2 in the presence of IHS is only marginally inhibited (about 20 per cent inhibition). The suppressor effect on CTLL-2 was not reversed by the addition of increasing doses of IL-2 (up to 100 U/ml) to cultures. The inhibition of the proliferative response of the CTLL-2 cells caused by IHS was also reversed by the addition of delipidated BSA. Our data suggest a role for fatty acids in the infected hamster serum-induced suppression of normal or L. donovani-infected cell proliferation.

Estado inmunitario del paciente pediátrico operado del corazón / Study the effect of open and closed-heart in the immune system of children

Se comunican los resultados de un estudio sobre el efecto de la cirugía de corazón abierto y cerrado en el estado inmunitario de pacientes pediátricos. El estudio se realizó en el Hospital Central Sur de Alta Especialidad (PEMEX) y en la unidad de cuidados intensivos pediátricos. El material de esta unidad de cuidados intensivos pediátricos. El material de estudio fueron 16 enfermos en quienes se realizó cirugía correctiva por enfermedad cardiaca congénita (con límite de edad de 16 meses y 14 años). La cuenta de leucocitos se encontró aumentada con linfopenia en el grupo de cirugía de corazón abierto y cerrado en forma significativa (p< 0.05), los niveles séricos de complemento (C3-C4) estuvieron altos, los de inmunoglobulinas IgG, IgA e IgM se encontraron bajos (p < 0.01). Dos pacientes resultaron con infección de la herida quirúrgica. Se concluye que la cirugía cardiovascular causa inmunodeficiencia transitoria con recuperación al quinto día del procedimiento

Transmission of dengue virus-specific suppressor signal depends on the presence of calcium.

The present study was undertaken to investigate the role of calcium in the production of dengue type 2 virus (DV) induced suppressor cytokine (SF) and in transmission of the suppressor signal via syngeneic macrophage (M phi) to recruit the second subpopulation of suppressor T(TS2) cell. Effect of calcium channel blocking drugs, Verapamil and Nifedipine, on the production and activity of SF was investigated. The production of SF was inhibited in a dose dependent manner by the calcium channel blockers. The suppressor activity of SF was also inhibited by calcium channel blocking drugs. SF could not be produced when spleen cells were cultured in a calcium free medium, the production being restored on substitution with calcium chloride. Treatment of M phi with the calcium channel blockers inhibited the transmission of the suppressor signal from TS1 to TS2 cells in a dose dependent manner. The influx of calcium during transmission of the suppressor signal was studied by measuring the 45Ca uptake. Calcium channel blocking drugs inhibited the 45Ca uptake by T lymphocytes. Thus, presence of calcium is obligatory for the production and suppressor activity of SF and it plays a critical role in transmission of the suppressor signal.

Procedimiento anestésico para el paciente canceroso tratado con radioterapia / mn anesthetic procedure for surgery in cancer patients who have been treated by radio-therapy

El efecto deletéreo que ocasiona la radioterapia en los diversos aparatos y sistemas del organismo es el factor clave que debe tomarse en consideración para establecer el estado anestésico en el paciente canceroso que necesita ser intervenido quirúrgicamente. Se resume el método terapéutico para realizar procedimiento de braquiterapia y para los enfermos que han sido tratados con anterioridad con quimioterapia y teleterapia. Los pacientes con cáncer tratados con quimioterapia, radiaciones y branquiterapia a menudo ameritan ser intervenidos quirúrgicamente bajo anestesia general o de conducción. Para establecer el estado anestésico deben de tenerse en cuenta los cambios hemodinámicos que ocasiona el propio tumor, así como la radioterapia y los procedimientos quirúrgicos anestésicos prescritos con anterioridad; los padecimientos concomitantes y los medicamentos recetados para su control; las condiciones generales de los individuos que siempre están deterioradas en forma importante; la necesidad de manipular las estructuras anatómicas ampliamente irrigadas y la dificultad para la intubación traqueal, ya sea porque la enfermedad involucra la cabeza y el cuello, o por la rigidez y el edema de la laringe, o por la dificultad para extender el cuello por radiaciones con antelación o por anquilosis temporomaxilar permanente

Molecular basis of Trypanosoma cruzi-induced immunosuppression. Altered expression by activated human lymphocytes of molecules which regulate antigen recognition and progression through the cell cycle

The mechanisms by which Trypanosoma cruzi causes dysfunction in normal human lymphocytes was studied by using an in vitro system in which purified parasites and normal peripheral blood mononuclear cells are co-cultured in the presence or absence of mitogens. Our results have shown that T. cruzi impairs the expression of receptors for interleukin-2 (IL-2R) and transferrin, activated lymphocyte membrane molecules which play key roles in controlling progression through the cell cycle. T. cruzi also downregulates the expression of constitutive lymphocyte molecules (e.g., CD4, and CD8) involved in the interactions between antigen-presenting cells and T lymphocytes as well as the expression of T cell receptor (TCR) and CD3 molecules. The latter molecular structures are physically associated and are responsible for signaling and transducing activation events resulting from antigen binding. Stimulated B lymphocytes also display reduced IL-2R expression in the presence of T. cruzi. In contrast, neither the expression of EA-1 molecules by T lymphocytes nor that of CD19 and CD20 molecules by B lymphocytes is affected by this parasite. Thus, the T. cruzi effects are selective, not indiscriminate. The activated T cell populations affected by T. cruzi show concomitant reductions in the levels of expression of IL-2R and CD4, IL-2R and CD8, IL-2R and CD3 or IL-2R and TCR as well as in their capacity to proliferate; 3H-thymidine uptake decreases and there is a massive arrest of cells at the G0/G1a phase of the cell cycle. The immunosuppressive effects of T. cruzi are reproduced by a protein molecule(s) released spontaneously by the parasite termed TIF (for trypanosomal immunosuppressive factor). We report herein that TIF does not compete with IL-2 for binding to IL-2R and that shedding of IL-2R is decreased in the presence of T. cruzi. Moreover, the intracellular level of IL-2R was found to be lower than that found in control cells cultured in the absence of parasites. These results suggest that suppressed IL-2R reflects a modification induced by T. cruzi at a time coinciding with or preceding IL-2R mRNA translation. Studies are underway to identify the earliest process targeted by T. cruzi

Appearance of adherent cells suppressive to erythropoiesis during an early stage of Plasmodium berghei infection in mice.

We examined the effect of adherent cells from bone marrow or spleen of mice infected with Plasmodium berghei on dyserythropoiesis. Significant reduction in number of erythroid progenitors (erythroid colony-forming units: CFU-E and erythroid burst-forming units: BFU-E) was observed in bone marrow as early as 1 day after P. berghei infection. When adherent cells were removed from bone marrow or spleen cells of infected mice, the number of CFU-E and BFU-E was clearly increased. Furthermore, addition of adherent cells from infected mice to nonadherent cells from normal mice inhibited erythroid colony formation significantly in a dose-dependent manner. These results suggest that the adherent cells obtained from bone marrow or spleen of mice in the early stage of P. berghei-infection have a suppressive effect on erythropoiesis.

Disminución de linfocitos T supresores y activación de monocitos y neutrófilos durante la reacción inmediata del asma-inducida por ejercicio / Lymphocyte T supressors dicrease and monocyte and neutrophil activation during the early reaction of exercise induced asthma

Durante la broncoconstricción inducida por el ejercicio (AIE) en individuos asmáticos se producen cambios cuantitativos y cualitativos de los leucocitos en sangre periférica. Para estudiar la participación de células inmunes y accesorias de la reacción inflamatoria en el AIE, analizamos las modificaciones de las subpoblaciones de linfocitos T y de la expresión de los antígenos de histocompatibilidad clase II (la) en monocitos, además de la participación de los receptores para el tercer factor del complemento (C36) mediante su expresión en monocitos y su adhesión y consecuente activación en neutrófilos. Se estudió 20 pacientes asmáticos alérgicos, de los cuales 11 presentaron broncoconstricción después de una prueba de ejercicio estandarizada. En todos los individuos estudiados se produjo, 5 min después del ejercicio, un aumento significativo de los leucocitos sanguíneos totales y de los neutrófilos, linfocitos y monocitos. Los basófilos y eosinófilos aumentaron sólo en los AIE (+). También este grupo presentó eosinófilos más altos desde el nivel inicial. En los individuos con AIE (+) el aumento inicial de los linfocitos a los 5 min se produce a expensas de los linfocitos T supresores (CD8) los que luego comienzan a disminuir hasta alcanzar valores significativamente menores que el inicial a los 60 min después del ejercicio. Esto lleva a un aumemto de la relación CD4/CD8 a nivel periférico, que es simultáneo con el aumento en la expresión de los antígenos Ia en monocitos observados en los AIE (+). Además en estos pacientes se encontró un aumento en la expresión de los receptores C3b en monocitos y en la producción de radical superóxido por neutrófilos estimulados con zimusán y complemento, desde el momento que se inicia la broncoconstricción hasta los 60 min después del ejercicio. Estos hallazgos sugieren que en los asmáticos con AIE (+) se producen cambios en las células inmunocompetentes que pudieran estar relacionados con la participación de células inflamatorias y su eventual manifestación como hiperactividad bronquial

Función inmunosupresora de las glicoproteínas de VIH-1, agente causal del SIDA / HIV-1 glycoprotein immunosuppression function

En este trabajo se demuestra que el virus VIH-1 inactivado por la luz ultravioleta inhibe la proliferación de linfocitos humanos estimulados con mitógenos; estos datos concuerdan con reportes de otros grupos. Además se observó que no es necesaria la presencia del virus completo ya que membranas celulares aisladas de células infectadas también tienen efecto supresor. Existen indicios de que la glicoproteína de transmembrana (gp41) de VIH-1 induce un efecto supresor, pero los experimentos aquí descritos usando gp41 purificada no pudieron confirmar esas observaciones. El efecto supresor de VIH-1 pudo ser bloqueado con anticuerpos monoclonales anti-CD4 (epitopio OKT4a) lo que implica que la interacción entre el receptor de los linfocitos T con la glicoproteína de superficie (gp120) juega un papel importante. Esto sugiere y confirma resultados de otros grupos que la gp120 tiene efecto inmunosupresor. Los sueros de pacientes positivos no mostraron efecto neutralizante sobre el virus aun cuando el suero contiene anticuerpos contra todas las proteínas estructurales del virus