RESUMEN
RESUMO O presente estudo analisa os efeitos da pandemia de Covid-19 sobre a saúde mental dos estudantes durante parte do período de suspensão das aulas presenciais. Trata-se de estudo transversal, aplicado entre outubro e dezembro de 2020, baseado em questionário on-line de autorrelato respondido por estudantes entre 13 e 20 anos, do 9º ano do Ensino Fundamental e do Ensino Médio, que acompanhavam as atividades escolares remotas em 21 escolas públicas estaduais e municipais, localizadas nas periferias dos municípios de São Paulo e Guarulhos. Para a análise dos dados, utilizaram-se dois modelos de regressão linear múltipla, tendo como variáveis dependentes os escores de depressão pelo Inventário de Depressão Infantil e de ansiedade pelo Scared (Screen for Child Anxiety Related Emotional Disorders). O tempo de exposição às telas, a inversão do sono e o sexo feminino, combinados com as dificuldades do ensino remoto e outros marcadores sociais (como cor/raça e casos de Covid-19 em casa), estão associados a sintomas de depressão e ansiedade durante a primeira onda da Covid-19 na Região Metropolitana de São Paulo, reforçando a importância da rotina escolar na vida desses jovens e os desafios colocados às escolas para a promoção da saúde mental dos estudantes no período pós-pandemia.
ABSTRACT This study analyzes the effects of the COVID-19 pandemic on students' mental health during part of the suspension of in-person classes. The study is a cross-sectional survey carried out from October2020 to December 2020. An online self-report questionnaire was answered by thirteen- to twenty-year old students, from the 9th grade (Middle School) to high school, who followed remote school activities in 21 state and municipal public schools located in peripheral areas of the cities of São Paulo and Guarulhos. Two linear regression models were used in the analysis, considering as dependent variables the depression scores as provided by the Child Depression Inventory and anxiety by the SCARED (Screen for Child Anxiety Related Emotional Disorders). The time of exposure to the screens, the inversion of sleep periods and the female gender, along with the difficulties of remote education and other social markers (such as color/race and cases of COVID-19 at home) are associated with symptoms of depression and anxiety during the first wave of the COVID-19 in the Metropolitan area of São Paulo. The findings reinforce the importance of school routine in the lives of those young people and the challenges posed to schools to promote students' mental health in the post-pandemic reality.
RESUMEN
The present study analyzes the effects of the Covid-19 pandemic on students' mental health during part of the suspension of the in-person classes. The study is a cross-sectional survey completed between October and December 2020. An online self-report questionnaire was answered by students between 13 and 20 years of age, from the 9th grade to high school, who followed remote school activities in 21 state and municipal public schools located in the suburbs of the municipalities of São Paulo and Guarulhos. Two linear regression models were used in the analysis, considering as dependent variables the depression scores by the Child Depression Inventory and anxiety by the SCARED (Screen for Child Anxiety Related Emotional Disorders). The time of exposure to the screens, the inversion of sleep, and the female gender, simultaneously with the difficulties of remote education and other social markers (such as color/race and cases of Covid-19 at home), are associated with symptoms of depression and anxiety during the first wave of the Covid-19 in the metropolitan area of São Paulo. The findings reinforce the importance of school routine in the lives of these young people and the challenges posed to schools to promote students' mental health in the post-pandemic reality.
O presente estudo analisa os efeitos da pandemia de Covid-19 sobre a saúde mental dos estudantes durante parte do período de suspensão das aulas presenciais. Trata-se de estudo transversal, aplicado entre outubro e dezembro de 2020, baseado em questionário online de autorrelato respondido por estudantes entre 13 e 20 anos, do 9º ano do Ensino Fundamental e do Ensino Médio, que acompanhavam as atividades escolares remotas em 21 escolas públicas estaduais e municipais, localizadas nas periferias dos municípios de São Paulo e Guarulhos. Para a análise dos dados, utilizou-se dois modelos de regressão linear múltipla, tendo como variáveis dependentes os escores de depressão pelo Inventário de Depressão Infantil e de ansiedade pelo SCARED (Screen for Child Anxiety Related Emotional Disorders). O tempo de exposição às telas, a inversão do sono e o sexo feminino, combinados com as dificuldades do ensino remoto e outros marcadores sociais (como cor/raça e casos de Covid-19 em casa), estão associados a sintomas de depressão e ansiedade durante a primeira onda da Covid-19 na região metropolitana de São Paulo, reforçando a importância da rotina escolar na vida desses jovens e os desafios colocados às escolas para a promoção da saúde mental dos estudantes no período pós-pandemia.
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Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptin-sufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.
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Inmunidad Innata/genética , Inflamación/genética , Leptina/genética , Lupus Eritematoso Sistémico/genética , Animales , Autoanticuerpos/biosíntesis , Autoanticuerpos/inmunología , Autoinmunidad/inmunología , Modelos Animales de Enfermedad , Humanos , Inmunidad Innata/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/patología , Leptina/antagonistas & inhibidores , Leptina/uso terapéutico , Lupus Eritematoso Sistémico/inducido químicamente , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Ratones , Ratones Endogámicos NZB , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Terpenos/toxicidadRESUMEN
Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection.
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Proteínas Protozoarias/inmunología , Vacunas Antiprotozoos/inmunología , Toxoplasma/inmunología , Toxoplasmosis/prevención & control , Vacunación , Animales , Encéfalo/parasitología , Células Cultivadas , Citocinas/sangre , Escherichia coli , Femenino , Inmunidad Celular , Inmunidad Humoral , Ratones Endogámicos C57BL , Proteínas Protozoarias/biosíntesis , Vacunas Antiprotozoos/biosíntesis , Toxoplasmosis/inmunología , Toxoplasmosis/parasitologíaRESUMEN
The proinflammatory activity of IL-17-producing Th17 cells has been associated with the pathogenesis of several autoimmune diseases. In this article, we provide direct evidence for a role of IL-17 in the pathogenesis of systemic lupus erythematosus (SLE). The induction of SLE by pristane in IL-17-sufficient wild-type mice did not occur in IL-17-deficient mice, which were protected from development of lupus autoantibodies and glomerulonephritis. The protection from SLE in IL-17-deficient mice was associated with a reduced frequency of CD3(+)CD4(-)CD8(-) double-negative T cells and an expansion of CD4(+) regulatory T cells, and did not depend on Stat-1 signaling. These data affirm the key role of IL-17 in the pathogenesis of SLE and strengthen the support for IL-17 blockade in the therapy of SLE.
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Autoanticuerpos/inmunología , Interleucina-17/inmunología , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/inmunología , Animales , Autoanticuerpos/sangre , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Interleucina-17/deficiencia , Interleucina-17/genética , Lupus Eritematoso Sistémico/inducido químicamente , Lupus Eritematoso Sistémico/genética , Nefritis Lúpica/sangre , Nefritis Lúpica/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NZB , Ratones Endogámicos , Ratones Noqueados , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Terpenos , Células Th17/inmunología , Células Th17/metabolismoRESUMEN
The heat shock protein of Toxoplasma gondii (TgHSP70) is a parasite virulence factor that is expressed during T. gondii stage conversion. To verify the effect of dexamethasone (DXM)-induced infection reactivation in the TgHSP70-specific humoral immune response and the presence of the protein in the mouse brain, we produced recombinant TgHSP70 and anti-TgHSP70 IgY antibodies to detect the protein, the specific antibody and levels of immune complexes (ICs) systemically, as well as the protein in the brain of resistant (BALB/c) and susceptible (C57BL/6) mice. It was observed higher TgHSP70-specific antibody titers in serum samples of BALB/c compared with C57BL/6 mice. However, the susceptible mice presented the highest levels of TgHSP70 systemically and no detection of specific ICs. The DXM treatment induced increased parasitism and lower inflammatory changes in the brain of C57BL/6, but did not interfere with the cerebral parasitism in BALB/c mice. Additionally, DXM treatment decreased the serological TgHSP70 concentration in both mouse lineages. C57BL/6 mice presented high expression of TgHSP70 in the brain with the progression of infection and under DXM treatment. Taken together, these data indicate that the TgHSP70 release into the bloodstream depends on the death of the parasites mediated by the host immune response, whereas the increased TgHSP70 expression in the brain depends on the multiplication rate of the parasite.
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Encéfalo/inmunología , Replicación del ADN/inmunología , Proteínas HSP70 de Choque Térmico/inmunología , Inmunidad Humoral/inmunología , Parásitos/inmunología , Toxoplasma/inmunología , Toxoplasmosis Animal/inmunología , Animales , Encéfalo/parasitología , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Toxoplasmosis Animal/parasitologíaRESUMEN
OBJECTIVE: Lupus nephritis depends on autoantibody deposition and activation of multiple immune cell types that promote kidney inflammation, including lymphocytes and monocyte/macrophages. Laquinimod, currently in clinical trials for multiple sclerosis and lupus nephritis, reduces infiltration of inflammatory cells into the spinal cord in experimental autoimmune encephalomyelitis. Activated monocyte/macrophages infiltrate the kidneys during nephritis in systemic lupus erythematosus (SLE). We undertook this study to determine whether using laquinimod to reduce monocyte/macrophage-driven tissue damage as well as to alter lymphocytes in SLE nephritis could have greater therapeutic benefit than current treatments that primarily affect lymphocytes, such as mycophenolate mofetil (MMF). METHODS: To test laquinimod efficacy, we used the (NZB × NZW)F1 mouse model of SLE, in which disease manifests as nephritis. Preventive and therapeutic studies were performed to determine whether laquinimod could prevent or delay nephritis, as measured by proteinuria, serum creatinine, survival, and renal pathology. Spleen and kidney leukocyte populations and suppression assays were analyzed by flow cytometry. RESULTS: Laquinimod prevented or delayed lupus manifestations at levels equal to or better than MMF. Laquinimod treatment was associated with reduced numbers of monocyte/macrophages, dendritic cells, and lymphocytes, as well as with induction of myeloid-derived suppressor cells in spleens and kidneys. Laquinimod suppressed macrophage-secreted tumor necrosis factor α and induced production of interleukin-10 (IL-10). In addition, laquinimod suppressed interferon-γ and IL-17 production by lymphocytes and down-regulated expression of activation/costimulatory markers on antigen-presenting cells. CONCLUSION: The effects of laquinimod on myeloid and lymphoid cells may contribute to improvements in (NZB × NZW)F1 mouse survival, proteinuria, and glomerulonephritis. Future development of laquinimod as a therapeutic agent for lupus nephritis is promising.
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Nefritis Lúpica/tratamiento farmacológico , Linfocitos/efectos de los fármacos , Células Mieloides/efectos de los fármacos , Quinolonas/uso terapéutico , Animales , Modelos Animales de Enfermedad , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Nefritis Lúpica/inmunología , Nefritis Lúpica/prevención & control , Linfocitos/inmunología , Linfocitos/metabolismo , Ratones , Células Mieloides/inmunología , Células Mieloides/metabolismo , Quinolonas/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: An increased frequency of atherosclerosis (ATH) in systemic lupus erythematosus (SLE) is well-documented but not fully explained by the presence of traditional cardiac risk factors. Several nontraditional biomarkers, including proinflammatory high-density lipoprotein (piHDL) and leptin, have been individually associated with subclinical ATH in SLE. The aim of this study was to examine whether these and other biomarkers can be combined into a risk profile, the Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular Disease in Patients with SLE (PREDICTS), that could be used to better predict future progression of ATH. METHODS: In total, 210 patients with SLE and 100 age-matched healthy control subjects (all women) participated in this prospective cohort study. The longitudinal presence of carotid plaque and intima-media thickness (IMT) were measured at baseline and followup (mean ± SD 29.6 ± 9.7 months). RESULTS: At followup, carotid plaque was present in 29% of SLE patients. Factors significantly associated with plaque, determined using Salford Predictive Modeling and multivariate analysis, included age ≥48 years (odds ratio [OR] 4.1, P = 0.002), high piHDL function (OR 9.1, P < 0.001), leptin levels ≥34 ng/dl (OR 7.3, P = 0.001), plasma soluble TWEAK levels ≥373 pg/ml (OR 28.8, P = 0.004), and history of diabetes (OR 61.8, P < 0.001). Homocysteine levels ≥12 µmoles/liter were also a predictor. However, no single variable demonstrated an ideal combination of good negative predictive values (NPVs), positive predictive values (PPVs), sensitivity, and specificity. A high-risk PREDICTS profile was defined as ≥3 positive biomarkers or ≥1 positive biomarker plus a history of diabetes; for high-risk SLE patients, the PPV was 64%, NPV was 94%, sensitivity was 89%, and specificity was 79%. In multivariate analysis, SLE patients with the high-risk profile had 28-fold increased odds for the longitudinal presence of plaque (P < 0.001) and increased progression of IMT (P < 0.001). CONCLUSION: A high-risk PREDICTS score confers 28-fold increased odds of the presence of any current, progressive, or acquired carotid plaque, both in patients with SLE and in control subjects, and is significantly associated with higher rates of IMT progression.
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Biomarcadores/sangre , Enfermedades de las Arterias Carótidas/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Adiponectina/sangre , Adulto , Factores de Edad , Apolipoproteína A-I/sangre , Aterosclerosis/sangre , Aterosclerosis/complicaciones , Aterosclerosis/diagnóstico , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/complicaciones , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , HDL-Colesterol/sangre , HDL-Colesterol/inmunología , LDL-Colesterol/sangre , Estudios de Cohortes , Citocina TWEAK , Complicaciones de la Diabetes , Diabetes Mellitus , Progresión de la Enfermedad , Femenino , Homocisteína/sangre , Humanos , Leptina/sangre , Estudios Longitudinales , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Placa Aterosclerótica/sangre , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/diagnóstico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Factores de Necrosis Tumoral/sangreRESUMEN
INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. Previous studies have suggested that interferon-lambda 1 (IFN-λ1), a type III interferon, plays an immunomodulatory role. In this study we investigated its role in SLE, including its correlation with disease activity, organ disorder and production of chemokines. METHODS: We determined levels of IFN-λ1 mRNA in peripheral blood mononuclear cells (PBMC) and serum protein levels in patients with SLE using real-time polymerase chain reaction (real-time PCR) and enzyme-linked immunoassay (ELISA). Further, we detected the concentration of IFN-inducible protein-10 (IP-10), monokine induced by IFN-γ (MIG) and interleukin-8 (IL-8) secreted by PBMC under the stimulation of IFN-λ1 using ELISA. RESULTS: IFN-λ1 mRNA and serum protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease showed higher IFN-λ1 mRNA and serum protein levels compared with those with inactive disease as well. Serum IFN-λ1 levels were positively correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), anti-dsDNA antibody, C-reactive protein (CRP) and negatively correlated with complement 3. Serum IFN-λ1 levels were higher in SLE patients with renal involvement and arthritis compared with patients without the above-mentioned manifestations. IFN-λ1 with different concentrations displayed different effects on the secretion of the chemokines IP-10, MIG and IL-8. CONCLUSIONS: These findings indicate that IFN-λ1 is probably involved in the renal disorder and arthritis progression of SLE and associated with disease activity. Moreover, it probably plays an important role in the pathogenesis of SLE by stimulating secretion of the chemokines IP-10, MIG and IL-8. Thus, IFN-λ1 may provide a novel research target for the pathogenesis and therapy of SLE.
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Quimiocinas/inmunología , Interleucinas/sangre , Interleucinas/inmunología , Leucocitos Mononucleares/inmunología , Lupus Eritematoso Sistémico/inmunología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Células Cultivadas , Quimiocina CXCL10/inmunología , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/inmunología , Quimiocina CXCL9/metabolismo , Quimiocinas/metabolismo , Femenino , Humanos , Inmunomodulación/inmunología , Interferón gamma/sangre , Interferón gamma/inmunología , Interferones , Interleucina-8/inmunología , Interleucina-8/metabolismo , Interleucinas/genética , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Nefritis Lúpica/inmunología , Nefritis Lúpica/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Adulto JovenRESUMEN
The present research investigated the influence of temperature and time of larvae culture on the infectivity of Strongyloides venezuelensis. Mice were infected s.c. with 1500 larvae of S. venezuelensis maintained at 28 °C for three days of culture (dc), 28 °C for seven dc or 18 °C for seven dc. On days 1, 3, 5, 7, 14 and 21 post-infection the animals were sacrificed and cell numbers in the blood, peritoneal cavity fluid (PCF), broncoalveolar fluid (BALF), cytokines, immunoglobulins, number of parasites and eggs/g of feces were quantified. Results demonstrated an increase in eosinophils and mononuclear cells in the blood, PCF and BALF of infected mice. Larvae at 28 °C/3dc induced earlier eosinophils in the PCF and BALF as opposed to larvae at 28 °C/7dc and 18 °C/7dc. Larvae at 28 °C/7dc induced higher synthesis of IL-4, IL-5 and IL-10 on days 5 and 7 post-infection. Larvae at 28 °C/3dc in culture induced higher synthesis of IL-12 than larvae of seven dc, but time in culture induced better synthesis of IFN-γ after larval migration had ceased and only adult worms were present. Larvae at 28 °C/3dc in culture induced higher synthesis of IgG and IgG1 and expelled less female parasites than larvae cultivated for seven days. In conclusion, it was observed that the infectivity of S. venezuelensis is influenced by variations in temperature and time of culture.
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Strongyloides/fisiología , Estrongiloidiasis/parasitología , Animales , Anticuerpos Antihelmínticos/sangre , Recuento de Células Sanguíneas , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/parasitología , Citocinas/análisis , Eosinófilos/citología , Heces/parasitología , Femenino , Inmunoglobulina G/sangre , Leucocitos Mononucleares/citología , Masculino , Ratones , Recuento de Huevos de Parásitos , Cavidad Peritoneal/citología , Cavidad Peritoneal/parasitología , Ratas , Ratas Wistar , Sigmodontinae , Strongyloides/inmunología , Temperatura , Factores de TiempoRESUMEN
The suppressive/immunomodulatory function of CD4(+)CD25(+)FOXP3(+) regulatory T (Treg) cells is crucial for the maintenance of immune homeostasis, which helps to prevent autoimmunity and reduce the inflammation induced by pathogens and environmental insults. This review summarizes the current knowledge on the types and mechanisms of action of Treg cells and their role in the immune tolerance to self-antigens, with a particular focus on naturally occurring Treg cells.
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Autoinmunidad , Inmunomodulación , Autotolerancia , Linfocitos T Reguladores/inmunología , Animales , Autoantígenos , Enfermedades Autoinmunes/inmunología , Antígenos CD4/análisis , Factores de Transcripción Forkhead/análisis , Humanos , Inflamación , Subunidad alfa del Receptor de Interleucina-2/inmunología , Ratones , Linfocitos T Reguladores/metabolismoRESUMEN
The contribution of inflammation to neurodegenerative diseases is increasingly recognized, but the role of inflammation in sporadic amyotrophic lateral sclerosis (sALS) is not well understood and no animal model is available. We used enzyme-linked immunosorbent assays (ELISAs) to measure the cytokine interleukin-17A (IL-17A) in the serum of ALS patients (n = 32; 28 sporadic ALS (sALS) and 4 familial ALS (fALS)) and control subjects (n = 14; 10 healthy subjects and 4 with autoimmune disorders). IL-17A serum concentrations were 5767 ± 2700 pg/ml (mean ± SEM) in sALS patients and 937 ± 927 pg/ml in fALS patients in comparison to 7 ± 2 pg/ml in control subjects without autoimmune disorders (p = 0.008 ALS patients vs. control subjects by Mann-Whitney test). Sixty-four percent of patients and no control subjects had IL-17A serum concentrations > 50 pg/ml (p = 0.003 ALS patients vs. healthy subjects by Fisher's exact test). The spinal cords of sALS (n = 8), but not control subjects (n = 4), were infiltrated by interleukin-1ß- (IL-1ß-), and tumor necrosis factor-α-positive macrophages (co-localizing with neurons), IL-17A-positive CD8 cells, and IL-17A-positive mast cells. Mononuclear cells treated with aggregated forms of wild type superoxide dismutase-1 (SOD-1) showed induction of the cytokines IL-1ß, interleukin-6 (IL-6), and interleukin-23 (IL-23) that may be responsible for induction of IL-17A. In a microarray analysis of 28,869 genes, stimulation of peripheral blood mononuclear cells by mutant superoxide dismutase-1 induced four-fold higher transcripts of interleukin-1α (IL-1α), IL-6, CCL20, matrix metallopeptidase 1, and tissue factor pathway inhibitor 2 in mononuclear cells of patients as compared to controls, whereas the anti-inflammatory cytokine interleukin-10 (IL-10) was increased in mononuclear cells of control subjects. Aggregated wild type SOD-1 in sALS neurons could induce in mononuclear cells the cytokines inducing chronic inflammation in sALS spinal cord, in particular IL-6 and IL-17A, damaging neurons. Immune modulation of chronic inflammation may be a new approach to sALS.
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Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/inmunología , Linfocitos T CD8-positivos/inmunología , Interleucina-17 , Mastocitos/inmunología , Médula Espinal/citología , Médula Espinal/inmunología , Superóxido Dismutasa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/patología , Estudios Transversales , Citocinas/sangre , Citocinas/inmunología , Femenino , Perfilación de la Expresión Génica , Humanos , Interleucina-17/sangre , Interleucina-17/inmunología , Macrófagos/citología , Macrófagos/inmunología , Masculino , Mastocitos/citología , Persona de Mediana Edad , Mutación , Médula Espinal/patología , Superóxido Dismutasa/genética , Superóxido Dismutasa-1RESUMEN
The aim of this study was to define the immunoregulatory role of prostaglandins in a mouse model of Strongyloides venezuelensis infection. Strongyloides venezuelensis induced an increase of eosinophils and mononuclear cells in the blood, peritoneal cavity fluid, and bronchoalveolar lavage fluid. Treatment with the dual cyclooxygenase (COX-1/-2) inhibitors indomethacin and ibuprofen, and the COX-2-selective inhibitor celecoxib partially blocked these cellular responses and was associated with enhanced numbers of infective larvae in the lung and adult worms in the duodenum. However, the drugs did not interfere with worm fertility. Cyclooxygenase inhibitors also inhibited the production of the T-helper type 2 (Th2) mediators IL-5, IgG1, and IgE, while indomethacin alone also inhibited IL-4, IL-10, and IgG2a. Cyclooxygenase inhibitors tended to enhance the Th1 mediators IL-12 and IFN-gamma. This shift away from Th2 immunity in cyclooxygenase inhibitor-treated mice correlated with reduced prostaglandin E(2) (PGE(2)) production in infected duodenal tissue. As PGE(2) is a well-characterized driver of Th2 immunity, we speculate that reduced production of this lipid might be involved in the shift toward a Th1 phenotype, favoring parasitism by S. venezuelensis. These findings provide new evidence that cyclooxygenase-derived lipids play a role in regulating host defenses against Strongyloides, and support the exploration of eicosanoid signaling for identifying novel preventive and therapeutic modalities against these infections.
Asunto(s)
Dinoprostona/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Strongyloides/inmunología , Estrongiloidiasis/inmunología , Animales , Líquido Ascítico/citología , Líquido Ascítico/inmunología , Sangre/inmunología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Celecoxib , Duodeno/parasitología , Inhibidores Enzimáticos/administración & dosificación , Eosinófilos/inmunología , Ibuprofeno/administración & dosificación , Indometacina/administración & dosificación , Leucocitos Mononucleares/inmunología , Pulmón/parasitología , Masculino , Ratones , Pirazoles/administración & dosificación , Ratas , Ratas Wistar , Strongyloides/patogenicidad , Estrongiloidiasis/patología , Sulfonamidas/administración & dosificación , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
This study evaluated selected limnological variables in inlet water in six sequentially distributed semi-intensive fishponds. Data were collected during 15 consecutive days in three distinct grow-out periods (May, October and January). Only phosphorus and pH varied among sites and periods (p 0.05) occurred in the cases of nitrite and dissolved oxygen. No variation was reported with regard to dissolved oxygen, conductivity, alkalinity, free CO2, bicarbonate, chlorophyll-a, nitrite and ammonia did not vary throughout the period (p > 0.05). In May, or rather, the final grow-out period, the fishponds displayed high concentrations, mainly in nitrogen compounds. As from fishpond 3, the inlet water contained high levels of nutrients. The water is passed from pond to pond, evidencing the need for management practices adequate to the specific conditions of each pond. Water quality should be monitored more frequently during high grow-out period when food addition is more intense. Thereafter, more care should be taken, as highest phosphorus concentrations occurred in May.
Este estudo verificou algumas variáveis limnológicas na água de entrada em seis viveiros de criação semi-intensiva de peixes com distribuição sequencial de água em três períodos distintos de engorda de peixes (maio, outubro e janeiro), durante 15 dias consecutivos em cada período. Somente o fósforo e pH variaram entre os pontos e períodos de coleta (p 0,05) ocorreu com nitrito e oxigênio dissolvido. Ao longo do período não foram significativas (p > 0,05) as variáveis como oxigênio dissolvido, condutividade, alcalinidade, CO2 livre, bicarbonato, clorofila-a, nitrito e amônia. No mês de maio, correspondente ao final do período de engorda de peixes, os viveiros apresentaram em geral maiores concentrações, principalmente, em relação aos compostos nitrogenados. A partir do viveiro 3 a água de entrada apresentou teores mais elevados de nutrientes em função da passagem direta de água de um viveiro para o outro, evidenciando a necessidade de práticas de manejo voltadas para as condições específicas de cada viveiro. A qualidade da água dos viveiros deve ser monitorada mais frequentemente, durante o período de engorda dos peixes, porém, após este período cuidados devem ser tomados visto que em maio foram observadas as maiores concentrações de fósforo na água.
Asunto(s)
Animales , Peces , Caudal de AguaRESUMEN
This study evaluated selected limnological variables in inlet water in six sequentially distributed semi-intensive fishponds. Data were collected during 15 consecutive days in three distinct grow-out periods (May, October and January). Only phosphorus and pH varied among sites and periods (p < 0.01); the opposite (p > 0.05) occurred in the cases of nitrite and dissolved oxygen. No variation was reported with regard to dissolved oxygen, conductivity, alkalinity, free CO2, bicarbonate, chlorophyll-a, nitrite and ammonia did not vary throughout the period (p > 0.05). In May, or rather, the final grow-out period, the fishponds displayed high concentrations, mainly in nitrogen compounds. As from fishpond 3, the inlet water contained high levels of nutrients. The water is passed from pond to pond, evidencing the need for management practices adequate to the specific conditions of each pond. Water quality should be monitored more frequently during high grow-out period when food addition is more intense. Thereafter, more care should be taken, as highest phosphorus concentrations occurred in May
Este estudo verificou algumas variáveis limnológicas na água de entrada em seis viveiros de criação semi-intensiva de peixes com distribuição sequencial de água em três períodos distintos de engorda de peixes (maio, outubro e janeiro), durante 15 dias consecutivos em cada período. Somente o fósforo e pH variaram entre os pontos e períodos de coleta (p < 0,01) e o oposto (p > 0,05) ocorreu com nitrito e oxigênio dissolvido. Ao longo do período não foram significativas (p > 0,05) as variáveis como oxigênio dissolvido, condutividade, alcalinidade, CO2 livre, bicarbonato, clorofila-a, nitrito e amônia. No mês de maio, correspondente ao final do período de engorda de peixes, os viveiros apresentaram em geral maiores concentrações, principalmente, em relação aos compostos nitrogenados. A partir do viveiro 3 a água de entrada apresentou teores mais elevados de nutrientes em função da passagem direta de água de um viveiro para o outro, evidenciando a necessidade de práticas de manejo voltadas para as condições específicas de cada viveiro. A qualidade da água dos viveiros deve ser monitorada mais frequentemente, durante o período de engorda dos peixes, porém, após este período cuidados devem ser tomados visto que em maio foram observadas as maiores concentrações de fósforo na água.
RESUMEN
Cell-enzyme-linked immunosorbent assay (cell-ELISA) is an useful technique for the quantitative analysis of cell surface antigen expression that was developed on the basis of enzyme immunohistochemistry (EIH) and ELISA. Since its development, which was made possible by the establishment of monoclonal antibody technology, a wide range of cell types and surface molecules were analyzed by cell-ELISA. Here we show four variants of this method and provide a brief comparison of cell-ELISA with flow cytometry (FACS) and radioimmunobinding assay (RIA), which are other methods for the quantitative detection of cell-surface molecules. We describe step-by-step procedures for both direct and indirect cell-ELISA using either adherent or nonadherent live cells.
Asunto(s)
Antígenos de Superficie/análisis , Ensayo de Inmunoadsorción Enzimática/métodos , Animales , Antígenos/análisis , Antígenos/inmunología , Antígenos de Superficie/inmunología , Células Cultivadas , Citometría de Flujo/métodos , Humanos , Radioinmunoensayo/métodosRESUMEN
Leptin is a hormone whose central role is to regulate endocrine functions and to control energy expenditure. After the discovery that leptin can also have pro-inflammatory effects, several studies have tried to address - at the molecular level - the pathways involved in leptin-induced modulation of the immune functions in normal and pathologic conditions. The signaling events influenced by leptin after its binding to the leptin receptor have been under scrutiny in the past few years, and considerable experimental work has elucidated the consequences of leptin effects on immune cells. This review examines the biochemistry, function and regulation of leptin signaling in view of possible intervention on this molecule for a better management and therapy of immune-mediated diseases.
RESUMEN
In systemic lupus erythematosus (SLE), adaptive CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) suppress Th cells that help autoantibody (autoAb)-producing B cells. It is not known whether naturally occurring Tregs can directly suppress B cells in SLE without an intermediate suppression of Th cells. This aspect is important for its implications in the natural course of SLE, because most if not all of the clinical and pathologic effects in SLE are associated with a dysregulated production of autoAbs. In this study, we show that natural Tregs can inhibit B cell activity in vitro and in vivo in SLE through cell contact-mediated mechanisms that directly suppress autoAb-producing B cells, including those B cells that increase numerically during active disease. These results indicate that one way by which natural Tregs attempt to limit humoral autoimmunity in SLE is by directly targeting autoreactive B cells.
Asunto(s)
Linfocitos B/inmunología , Lupus Eritematoso Sistémico/inmunología , Linfocitos T Reguladores/inmunología , Animales , Formación de Anticuerpos , Autoanticuerpos/biosíntesis , Comunicación Celular/inmunología , Femenino , Humanos , Ratones , Linfocitos T Colaboradores-InductoresRESUMEN
Treatment of (NZB x NZW)F(1) (NZB/W) lupus-prone mice with the anti-DNA Ig-based peptide pConsensus prolongs the survival of treated animals and effectively delays the appearance of autoantibodies and glomerulonephritis. We have previously shown that part of these protective effects associated with the induction of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) that suppressed autoantibody responses. Because the effects of pConsensus appeared secondary to qualitative rather than quantitative changes in Tregs, we investigated the molecular events induced by tolerance in Tregs and found that signaling pathways including ZAP70, p27, STAT1, STAT3, STAT6, SAPK, ERK, and JNK were not significantly affected. However, peptide tolerization affected in Tregs the activity of the MAPK p38, whose phosphorylation was reduced by tolerance. The pharmacologic inhibition of p38 with the pyridinyl imidazole inhibitor SB203580 in naive NZB/W mice reproduced in vivo the effects of peptide-induced tolerance and protected mice from lupus-like disease. Transfer experiments confirmed the role of p38 in Tregs on disease activity in the NZB/W mice. These data indicate that the modulation of p38 activity in lupus Tregs can significantly influence the disease activity.