Caracterização de marcadores inflamatórios associados a pacientes com lúpus eritematoso sistêmico em tratamento

ResumoObjetivoCaracterizar os perfis inflamatórios de pacientes com lúpus eritematoso sistêmico (LES) que recebiam o tratamento padrão em comparação com controles saudáveis.Pacientes e métodosColetou‐se o sangue venoso periférico de pacientes com LES (n = 14) e controles (n = 18) no momento da entrada no estudo. As amostras de sangue foram usadas para quantificação, por citometria de fluxo, da expressão dos antígenos de superfície CD11b (integrina) e CXCR2 em neutrófilos e linfócitos, enquanto as citocinas foram avaliadas em amostras de soro. Avaliou‐se a capacidade dos neutrófilos purificados de fagocitar zimosan opsonizado com plasma humano.ResultadosOs pacientes apresentavam uma pontuação mediana (intervalo interquartil) no Sledai de 1 (0‐2), característica de pacientes em remissão. As concentrações séricas de IL‐6 e IL‐10 foram significativamente maiores no grupo de pacientes em comparação com os controles; o índice de fagocitose de neutrófilos circulantes estava significativamente reduzido nos pacientes em comparação com os controles. Os níveis de IL‐2, IL‐5, IL‐8 e TNF‐α não diferiram significativamente entre pacientes e controles. A análise da citometria de fluxo revelou que os níveis de expressão de CD11b estavam reduzidos nos linfócitos (mas não nos neutrófilos) obtidos de pacientes com LES, enquanto a expressão do receptor de superfície CXCR2 foi semelhante em neutrófilos e linfócitos.ConclusãoOs pacientes com LES que recebiam tratamento padrão apresentaram níveis sistêmicos elevados de IL‐6 e IL‐10, redução na capacidade fagocítica dos neutrófilos e redução da expressão de CD11b em linfócitos, mesmo quando os sintomas estavam em remissão. Essas alterações nos componentes da imunidade inata podem colocar esses indivíduos em maior risco de adquirir infecções.AbstractObjectiveTo characterize the inflammatory profiles of patients with systemic lupus erythematosus (SLE) receiving standard treatment compared to healthy controls.Patients and methodsPeripheral venous blood was collected from SLE patients (n = 14) and controls (n = 18) at enrollment. Blood samples were used for quantification, by flow cytometry, of CD11b (integrin) and CXCR2 expression surface antigen in neutrophils and lymphocytes, while cytokines were assayed in serum samples. Purified neutrophils were assayed by their ability to phagocytize human plasma‐opsonized zymosan.ResultsPatients had a median (interquartile range) SLEDAI score of 1.0 (0 ‐ 2.0) characteristic of patients in remission. IL‐6 and IL‐10 serum concentrations were significantly higher in the patient group compared to controls and the phagocytic index of circulating neutrophils was significantly reduced in patients compared to controls. The levels of IL‐2, IL‐5, IL‐8 and TNF‐ α did not significantly differ between patients and controls. Flow cytometric analysis revealed that the CD11b expression levels were reduced in lymphocytes (but not in neutrophils) obtained from SLE patients, while surface expression of the chemokine receptor CXCR2 was similar in both neutrophils and lymphocytes.ConclusionSLE patients receiving standard treatment presented with elevated systemic levels of IL‐6 and IL‐10, reduced neutrophil phagocytic capacity, and reduced lymphocyte expression of CD11b even when symptoms were in remission. These alterations to innate immune components may put these individuals at a greater risk for acquiring infections

Amblyomma sculptum Salivary PGE2 Modulates the Dendritic Cell-Rickettsia rickettsii Interactions in vitro and in vivo

Amblyomma sculptum is an important vector of Rickettsia rickettsii, causative agent of Rocky Mountain spotted fever and the most lethal tick-borne pathogen affecting humans. To feed on the vertebrate host's blood, A. sculptum secretes a salivary mixture, which may interact with skin resident dendritic cells (DCs) and modulate their function. The present work was aimed at depicting the A. sculptum saliva-host DC network and the biochemical nature of the immunomodulatory component(s) involved in this interface. A. sculptum saliva inhibits the production of inflammatory cytokines by murine DCs stimulated with LPS. The fractionation of the low molecular weight salivary content by reversed-phase chromatography revealed active fractions eluting from 49 to 55% of the acetonitrile gradient. Previous studies suggested that this pattern of elution matches with that observed for prostaglandin E2 (PGE2) and the molecular identity of this lipid mediator was unambiguously confirmed by a new high-resolution mass spectrometry methodology. A productive infection of murine DCs by R. rickettsii was demonstrated for the first time leading to proinflammatory cytokine production that was inhibited by both A. sculptum saliva and PGE2, a result also achieved with human DCs. The adoptive transfer of murine DCs incubated with R. rickettsii followed by treatment with A. sculptum saliva or PGE2 did not change the cytokine profile associated to cellular recall responses while IgG2a-specific antibodies were decreased in the serum of these mice. Together, these findings emphasize the role of PGE2 as a universal immunomodulator of tick saliva. In addition, it contributes to new approaches to explore R. rickettsii-DC interactions both in vitro and in vivo

Intervenção fisioterapêutica promove melhora na qualidade de vida de indivíduos com pênfigo

INTRODUÇÃO: O pênfigo é uma doença autoimune, caracterizada por vésico-bolhas cuja manifestações clínicas crônicas geram alterações na qualidade de vida. Existem relatos de pênfigo em vários continentes; porém ocorre predominantemente na região centro-norte da América do Sul. No Brasil, a doença predomina nos estados do Centro-Oeste e Sudeste. Objetivou-se avaliar o perfil e a qualidade de vida de pacientes com pênfigo em uma cidade brasileira, para intervenção fisioterapêutica. MÉTODOS: Foram analisados 15 prontuários de pacientes institucionalizados; contudo, 7 voluntários passaram por entrevista inicial e final por meio do questionário de qualidade de vida SF-36. Entremeio a coleta de dados, foram aplicados exercícios fisioterapêuticos durante o período de 4 meses. Após o período pré-determinado os dados foram comparados e analisados de forma quantitativa por meio do Med Calc E e teste T the student. RESULTADOS: Os 15 pacientes em tratamento tinham idade média de 40 anos; 53,3% eram melanoderma; o gênero masculino correspondia a 80%; 60% apresentam contato com zona rural e 80% são de origem da região sudeste. Os 7 pacientes que participaram da intervenção tenderam melhorar os domínios avaliados pelo SF-36 com exceção da vitalidade e aspectos sociais. CONCLUSÕES: O perfil da população deste hospital tem correlação com a literatura pesquisada. De acordo com o SF-36, houve melhora geral da qualidade de vida dos pacientes que aderiram às atividades propostas. Essa pesquisa sugere que a intervenção fisioterapêutica promove diferentes benefícios para os pacientes com pênfigo

Characterization of inflammatory markers associated with systemic lupus erythematosus patients undergoing treatment

ABSTRACT Objective: To characterize the inflammatory profiles of patients with systemic lupus erythematosus receiving standard treatment compared to healthy controls. Patients and methods: Peripheral venous blood was collected from systemic lupus erythematosus patients (n = 14) and controls (n = 18) at enrollment. Blood samples were used for quantification, by flow cytometry, of CD11b (integrin) and Chemokine receptor CXCR2 expression surface antigen in neutrophils and lymphocytes, while cytokines were assayed in serum samples. Purified neutrophils were assayed by their ability to phagocytize human plasma-opsonized zymosan. Results: Patients had a median (interquartile range) disease activity index of 1.0 (0-2.0) characteristic of patients in remission. Interleukin-6 and interleukin-10 serum concentrations were significantly higher in the patient group compared to controls and the phagocytic index of circulating neutrophils was significantly reduced in patients compared to controls. The levels of interleukin-2, interleukin-5, interleukin-8 and tumor necrosis factor alpha did not significantly differ between patients and controls. Flow cytometric analysis revealed that the integrin expression levels were reduced in lymphocytes (but not in neutrophils) obtained from systemic lupus erythematosus patients, while surface expression of the chemokine receptor 2 was similar in both neutrophils and lymphocytes. Conclusion: Systemic lupus erythematosus patients receiving standard treatment presented with elevated systemic levels of interleukin-6 and interleukin-10, reduced neutrophil phagocytic capacity, and reduced lymphocyte expression of integrin even when symptoms were in remission. These alterations to innate immune components may put these individuals at a greater risk for acquiring infections

Cytokine and Chemokines Alterations in the Endemic Form of Pemphigus Foliaceus (Fogo Selvagem)

IntroductionThe endemic form (fogo selvagem—FS) of pemphigus foliaceus is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-1. Despite the array of findings, the role of chemokines and cytokines that dictate the immune response and disease outcome is still poorly investigated.Materials and methodsSerum from 64 patients diagnosed with FS was used to draw and establish the levels of these molecules on this disease and establish the levels of these molecules with the severity of FS, and influence of treatment.ResultsIn comparison to healthy subjects, FS patients, newly diagnosed and still without therapeutic intervention, had higher levels of IL-22 and CXCL-8, and reduced levels of IFN-γ, IL-2, IL-15, and CCL-11. Furthermore, treatment using immunosuppressant drugs augmented the production of IFN-γ, IL-2, CCL-5, and CCL-11 besides reducing the levels of IL-22 and CXCL-10. Immunosuppressive therapy seemed to have long-lasting effects on the production of higher amounts of IFN-γ, IL-2, and CCL-5, besides keeping lowered the levels of IL-22 in remission FS patients.ConclusionTaken together, our findings suggest a putative role of IL-22 in the pathogenesis of FS. Finally, data presented here may contribute for better understanding the immune aspects that control disease outcome