Immunomodulation From Moderate Exercise Promotes Control of Experimental Cutaneous Leishmaniasis.

Physical exercise has been described as an important tool in the prevention and treatment of numerous diseases as it promotes a range of responses and adaptations in several biological systems, including the immune system. Studies on the effect of exercise on the immune system could play a critical role in improving public health. Current literature suggests that moderate intensity exercise can modulate the Th1/Th2 dichotomy directing the immune system to a Th1 cellular immune response, which favors the resolution of infections caused by intracellular microorganisms. Leishmaniasis is a group of diseases presenting a wide spectrum of clinical manifestations that range from self-limiting lesions to visceral injuries whose severity can lead to death. The etiological agents responsible for this group of diseases are protozoa of the genus Leishmania. Infections by the parasite Leishmania major in mice (Balb/c) provide a prototype model for the polarization of CD4+ T cell responses of both Th1 (resistance) or Th2 (susceptibility), which determines the progression of infections. The aim of this study was to evaluate the effect of exercise on the development of L. major experimental infections by scanning the pattern of immune response caused by exercise. Groups of Balb/c mice infected with L. major were divided into groups that preformed a physical exercise of swimming three times a week or were sedentary along with treatment or not with the reference drug, meglumine antimoniate. Animals in groups submitted to physical exercise did not appear to develop lesions and presented a significantly lower parasite load independent of drug treatment. They also showed a positive delayed hypersensitivity response to a specific Leishmania antigen compared to control animals. The IFN-γ/IL-4 and IFN-γ/IL10 ratios in trained animals were clearly tilted to a Th1 response in lymph node cells. These data suggest that moderate intensity exercise is able to modulate the Th1 response that provides a protective effect against the development of leishmanial lesions.

Effect of Exercise on Inflammatory Profile of Older Persons: Systematic Review and Meta-Analyses.

BACKGROUND: Inflammatory cytokines and acute phase proteins increase with aging, promoting a chronic low-grade inflammation. Studies have shown a positive effect of exercise on inflammatory markers in older persons. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) are the main biomarkers investigated. However, it is unclear if exercise could decrease all these biomarkers. PURPOSE: The aim was to analyze the effect of chronic exercise on IL-6, TNF-α, and CRP levels in older persons. METHODS: Preferred Reporting Items in Systematic Reviews and Meta-analyses guidelines were adopted. Original articles that investigated the effect of chronic exercise on inflammatory profile of the elderly persons were eligible for this review. The databases PubMed, PEDro, EBSCO, and BioMed Central were searched. Three reviewers evaluated each publication for reducing bias. Data about IL-6, TNF-α, and CRP were collected and analyzed. A standardized mean difference based on estimated pooled effect size was calculated considering heterogeneity index (I2) and random effect. RESULTS: Seventy-six studies were retrieved from databases, and 8 of them were analyzed. IL-6 and CRP levels decreased after chronic exercise (overall effect P < .05). CONCLUSION: Regular exercise decreases IL-6 and CRP levels in older persons. The effect of exercise on TNF-α remains unclear.

The Dialogue of the Host-Parasite Relationship: Leishmania spp. and Trypanosoma cruzi Infection.

The intracellular protozoa Leishmania spp. and Trypanosoma cruzi and the causative agents of Leishmaniasis and Chagas disease, respectively, belong to the Trypanosomatidae family. Together, these two neglected tropical diseases affect approximately 25 million people worldwide. Whether the host can control the infection or develops disease depends on the complex interaction between parasite and host. Parasite surface and secreted molecules are involved in triggering specific signaling pathways essential for parasite entry and intracellular survival. The recognition of the parasite antigens by host immune cells generates a specific immune response. Leishmania spp. and T. cruzi have a multifaceted repertoire of strategies to evade or subvert the immune system by interfering with a range of signal transduction pathways in host cells, which causes the inhibition of the protective response and contributes to their persistence in the host. The current therapeutic strategies in leishmaniasis and trypanosomiasis are very limited. Efficacy is variable, toxicity is high, and the emergence of resistance is increasingly common. In this review, we discuss the molecular basis of the host-parasite interaction of Leishmania and Trypanosoma cruzi infection and their mechanisms of subverting the immune response and how this knowledge can be used as a tool for the development of new drugs.

Interactions between Leishmania braziliensis and Macrophages Are Dependent on the Cytoskeleton and Myosin Va.

Leishmaniasis is a neglected tropical disease with no effective vaccines. Actin, microtubules and the actin-based molecular motor myosin Va were investigated for their involvement in Leishmania braziliensis macrophage interactions. Results showed a decrease in the association index when macrophages were without F-actin or microtubules regardless of the activation state of the macrophage. In the absence of F-actin, the production of NO in non-activated cells increased, while in activated cells, the production of NO was reduced independent of parasites. The opposite effect of an increased NO production was observed in the absence of microtubules. In activated cells, the loss of cytoskeletal components inhibited the release of IL-10 during parasite interactions. The production of IL-10 also decreased in the absence of actin or microtubules in non-activated macrophages. Only the disruption of actin altered the production of TNF-α in activated macrophages. The expression of myosin Va tail resulted in an acute decrease in the association index between transfected macrophages and L. braziliensis promastigotes. These data reveal the importance of F-actin, microtubules, and myosin-Va suggesting that modulation of the cytoskeleton may be a mechanism used by L. braziliensis to overcome the natural responses of macrophages to establish infections.

Efeito do exercício no sistema imune: resposta, adaptação e sinalização celular / Effect of exercise on immune system: response, adaptation and cell signaling

INTRODUÇÃO: Durante o último século, o homem tornou-se menos ativo fisicamente, adotando hábitos cada vez mais sedentários. Isto promoveu aumento na incidência de doenças crônicas tais como doenças cardiovasculares, diabetes do tipo 2 e síndrome metabólica. A prática de atividade física pode influenciar o estado de higidez alterando estados metabólicos e também o sistema imunológico. OBJETIVO: Revisar na literatura estudos que abordem os efeitos promovidos pelo exercício físico no desenvolvimento da resposta imunológica e suas possíveis vias de transdução de sinais. MÉTODOS: Foram consultadas as bases de dados SciELO e PubMed. RESULTADOS: A literatura disponível mostra que durante a prática de exercício, várias subpopulações de leucócitos são alteradas de acordo com a intensidade e duração da atividade desempenhada. Exercícios de intensidade moderada estimulam uma resposta pró-inflamatória, enquanto aqueles de alta intensidade tendem a promover respostas anti-inflamatórias visando diminuir os danos na musculatura esquelética. Tais alterações são vistas em células apresentadoras de antígeno (como macrófagos e células dendríticas), neutrófilos, células natural killers (NK) e em moléculas de superfície como os receptores do tipo Toll (TLR) e do complexo principal de histocompatibilidade de classe II (MHC II), além das modificações promovidas em todo o repertório de citocinas. CONCLUSÃO: O estado atual do conhecimento permite considerar que as alterações no sistema imune são dependentes dos parâmetros inerentes ao exercício e que para que todas estas alterações ocorram, algumas cascatas de sinalização celular são acionadas, dando origem a um complexo processo de fosforilação/desfosforilação que culmina em ativação de fatores de transcrição, tradução de RNAm, síntese proteica e proliferação celular.

INTRODUCTION: Over the last century, people have become less active, adopting more sedentary habits. This scenario has increased the incidence of chronic diseases such as cardiovascular diseases, type 2 diabetes and metabolic syndrome. The practice of physical activities can influence healthiness by altering the metabolic state and also the immune system. OBJECTIVE: To review the literature for studies that address the effects promoted by physical exercise on the development of immune responses and the possible signal transduction pathways. METHODS: The SciELO and PubMed data bases were consulted. RESULTS: The available literature shows that during the practice of exercise, various subpopulations of leukocytes are altered in accordance with the intensity and duration of the activity performed. Exercise of moderate intensity stimulates a pro-inflammatory response, while those of high intensity tend to promote anti-inflammatory responses with the purpose to decrease damage to skeletal muscle. Such alterations are observed in cells that present antigens (such as macrophages and dendritic cells), neutrophils, natural killer cells (NK) and in surface molecules like Toll-like receptors (TLR) and major histocompatibility complex class II, as well as the entire repertoire of cytokines. CONCLUSION: The current state of knowledge suggests that the alterations in the immune system are dependent on parameters inherent to exercise and that in order to have all these alterations occurring, some cell signaling cascades are activated, giving rise to a complex process of phosphorylation/dephosphorylation that culminates in the activation of transcription factors, translation of mRNA's, protein synthesis and cell proliferation.

Estudio de la epidemiología de la Maternidad del HCUCh, para decidir sobre acciones en temas prioritarios / Epidemiologic study of the maternity HCUCh, in order to decide on actions in high-priority subjects

La gestión clínica eficiente de los servicios de salud requiere del conocimiento exacto de la epidemiología local, con el objeto de enfrentar y solucionar los problemas prioritarios. Nos propusimos confeccionar un sistema de recopilación de datos y de análisis de los mismos que permita conocer la frecuencia relativa de patologías obstétricas, calcular indicadores de salud y evaluar la calidad de atención de la maternidad del Hospital Clínico de la Universidad de Chile. Se identificaron las prestaciones de salud obstétricas más frecuentes y se diseñó una base de datos clínicos. Se realizó un registro completo de los antecedentes clínicos en la ficha de cada paciente al momento de su primera consulta, durante su hospitalización y al finalizar la atención obstétrica. Posteriormente los resultados fueron analizados según frecuencia relativa y sometidos a comparación con los indicadores de salud de los servicios de atención públicos. Durante el año 2003, se efectuaron 11873 consultas ambulatorias, de las cuales el 39 por ciento fueron catalogadas como de alto riesgo obstétrico. En nuestra Unidad de Alto Riesgo Obstétrico se realizaron 355 egresos hospitalarios, de los cuales el 54,92 por ciento correspondieron a embarazos mayores de 28 semanas. Un total de 1665 nacimientos fueron atendidos en nuestra maternidad, de los cuales el 60,7 por ciento correspondieron a partos vaginales y un 39,3 por ciento a cesáreas. La frecuencia relativa de patología obstétrica y los indicadores de salud de la Maternidad del Hospital Clínico de la Universidad de Chile son similares a los encontrados dentro de los servicios de atención pública del país. La creación e implementación de bases de datos clínicos es un método eficiente de almacenamiento de información que permite un análisis cuantitativo y cualitativo de la atención obstétrica.