Cytokine production in allergic and Trichuris trichiura-infected children from an urban region of the Brazilian northeast.

The relationship between the cellular immune response during Trichuris trichiura infection and asthma has not yet been established. In this study, the cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17A were evaluated in asthmatic children harboring T. trichiura. For this assessment, asthmatic and non-asthmatic children (ISAAC questionnaire) were submitted to parasitological tests and blood samples were cultured (mitogen stimulation) for cytokine measurements in the supernatant. Asthma frequencies were similar in infected and uninfected children, but IL-4, IL-6, TNF-α and IL-10 levels were high in the infected asthmatic children. Additionally, infected non-asthmatic children exhibited high levels of these cytokines in relation to uninfected non-asthmatic children; however, cytokine levels were lower when compared with infected and asthmatic children. Therefore, T. trichiura infection positively modulated the pro- and anti-inflammatory cytokines in asthmatic children, but a background of asthma seemed to narrow the production of cytokines induced by this helminth.

Giardia lamblia e alergia respiratória: estudo em uma amostra de crianças de área urbana com frequência elevada da protozoose / Giardia lamblia and respiratory allergies: a study of children from an urban area with a high incidence of protozoan infections

OBJETIVO: Uma elevada incidência de enteroparasitoses é encontrada em regiões urbanas do nordeste brasileiro. As infecções por Giardia lamblia têm sido relacionadas com aumento da prevalência de alergias cutâneas e gastrointestinais. Contudo, ainda existe pouca informação sobre a associação entre a giardíase e doenças alérgicas das vias aéreas. Diante disso, o presente estudo se propôs a verificar a relação entre a infecção por G. lamblia em crianças de área urbana e reatividade alérgica respiratória. MÉTODOS: O estudo incluiu 110 pacientes, de ambos os sexos e idades, entre 5 e 15 anos. Os pacientes foram submetidos a questionários de avaliação dos sintomas clínicos, testes cutâneos de leitura imediata e exames coproparasitológicos e sorológicos. RESULTADOS: Foi verificada uma frequência elevada de crianças infectadas por G. lamblia (45%, 50/110). A infecção pelo protozoário não foi associada com maior risco de alergias respiratórias (p = 0,075), elevação de IgE total (p = 0,701), IgE específica (p = 0,250) ou teste cutâneo positivo para diferentes alérgenos ambientais (p = 0,239). CONCLUSÃO: O estudo demonstrou que a presença dos sintomas de asma, atopia cutânea e marcadores sorológicos não foram associados com a presença de infecção pela G. lamblia nessa amostra de crianças.

OBJECTIVES: There is a high incidence of intestinal parasite infection in urban areas in the Northeast of Brazil. Giardia lamblia infections have been associated with increased prevalence of cutaneous allergies and gastrointestinal disorders. However, little is known about the relationship between giardiasis and allergic diseases of the airways. The present study aimed to investigate the possible association between respiratory allergic diseases and infections by G. lamblia in children from urban areas. METHODS: This study recruited 110 patients of both sexes aged 5-15 years. Patients were administered a questionnaire evaluating clinical symptoms and were given skin tests, parasite tests and serum tests. RESULTS: A high incidence of G. lamblia was observed (45%, 50/110). Infections by this protozoan were not associated with increased risk of respiratory allergy (p = 0.075), high total IgE levels (p = 0.701), positive specific IgE tests (p = 0.250), or positive skin tests for a range of environmental allergens (p = 0.239). CONCLUSION: This study demonstrated that symptoms of asthma, skin allergy and serum markers were not associated with G. lamblia infections in this sample of children from urban areas.

Associação dos polimorfismos nos genes da IL-4, IL-5, IL-13 e IL-10 e a asma infantil: uma revisão sistemática / Association of polymorphisms in IL-4, IL-5, IL-13 or IL-10 genes and childhood asthma: a systematic review

Objetivo: A reação inflamatória observada na asma é decorrente da ativação de linfócitos Th2, ação das citocinas IL-4, IL-5, IL-9 e IL-13 e produção de IgE. Estima-se que diferentes genes e seus polimorfismos influenciam o desenvolvimento da doença. O presente estudo apresenta os resultados de artigos, selecionados sistematicamente, sobre a associação de polimorfismos nos genes da IL-4, IL-5, IL-13 e IL-10 e o fenótipo de asma, gravidade da doença e atopia em crianças. Fontes dos dados: Foi realizada uma pesquisa por artigos nos principais bancos científicos e foram selecionados 15 trabalhos, publicados entre 1999 e 2008. Síntese dos dados: Em relação à associação entre os polimorfismos, em diferentes regiões do gene e o diagnóstico clínico de asma, foi verificado que para IL-4, 50% (4/8) dos artigos observaram associação significativa e para IL-13, 80% (4/5). Contudo, os estudos para os genes da IL-5 e IL-10 não encontraram associação positiva. Para a variável níveis de gravidade e/ou presença de atopia, 67% (4/6) e 100% (5/5) dos estudos encontraram associação nos genes da IL-4 e da IL-13, respectivamente. Para os genes da IL-5 e IL-10 foi observada associação significativa, porém, não é possível inferir conclusões, devido o pequeno número de artigos disponíveis. Conclusões: Os resultados desta revisão sistemática ressaltam a participação de polimorfismos nos genes da IL-4 e IL-13 na indução de níveis de asma, gravidade dos sintomas e/ou atopia, além de enfatizar a necessidade de mais estudos sobre a participação do polimorfismo da IL-5 e IL-10 com os diferentes níveis de asma.

Objective: The inflammatory reaction observed in asthma is due to the activation of Th2 lymphocytes, the action of cytokines IL-4, IL-5, IL-9 and IL-13 and the production of IgE. It is estimated that different genes and their polymorphisms influence the development of the disease. This study presents the results of systematically selected articles about the association of polymorphisms in genes of cytokines IL-4, IL-5, IL-13, IL-10 and asthma phenotype, the disease severity and atopy in children. Data source: 15 scientific articles published between 1999 and 2008 were selected from major databases. Data synthesis: Regarding the association between polymorphisms in different gene regions and the clinical diagnosis of asthma, 50% (4/8) of the articles about IL-4 stated the existence of a significant association and 80% (4/ 5) of those that studied IL-13 presented the same conclusion. However, in studies about genes of IL-5 and IL-10 no positive associations were found. For the variable levels of severity and/or the existence of atopy, 67% (4/6) and 100% (5/5) of the studies showed an association with genes of IL-4 and IL-13, respectively. Regarding genes of IL-5 and IL-10, a significant association was observed, but it was not possible to point out conclusions, due to the poor number of articles available. Conclusions: The results of this systematic review highlight the role of polymorphisms in genes of IL-4 and IL-13 in the induction of asthma phenotypes, severity of symptoms and/or atopy. Also, this review emphasizes the need for further studies about the participation of polymorphisms of IL-5 and IL-10 in the different asthma phenotypes.

Giardia lamblia and respiratory allergies: a study of children from an urban area with a high incidence of protozoan infections.

OBJECTIVES: There is a high incidence of intestinal parasite infection in urban areas in the Northeast of Brazil. Giardia lamblia infections have been associated with increased prevalence of cutaneous allergies and gastrointestinal disorders. However, little is known about the relationship between giardiasis and allergic diseases of the airways. The present study aimed to investigate the possible association between respiratory allergic diseases and infections by Giardia lamblia in children from urban areas. METHODS: This study recruited 110 patients of both sexes aged 5-15 years. Patients were administered a questionnaire evaluating clinical symptoms and were given skin tests, parasite tests and serum tests. RESULTS: A high incidence of Giardia lamblia was observed (45%, 50/110). Infections by this protozoan were not associated with increased risk of respiratory allergy (p = 0.075), high total IgE levels (p = 0.701), positive specific IgE tests (p = 0.250), or positive skin tests for a range of environmental allergens (p = 0.239). CONCLUSION: This study demonstrated that symptoms of asthma, skin allergy and serum markers were not associated with Giardia lamblia infections in this sample of children from urban areas.

Cytotoxic, antitumor and leukocyte migration activities of resveratrol and sitosterol present in the hidroalcoholic extract of Cissus sicyoides L., Vitaceae, leaves

Cissus sicyoides L. pertains to the Vitaceae family. It is popularly known as "insulina, cipo-pucá, bejuco caro, puci, anil trepador". A vasoconstrictor effect and an antibacterial activity have also been allocated to it. In Brazil, C. sicyoides was evaluated for its anticonvulsant and anti-diabetc properties. Phytochemistry studies identified and isolated sitosterol and resveratrol compounds from its aerial parts which are pointed out as having antitumor activities. The goal of this study was to investigate the cytotoxic and antitumor activities of Cissus sicyoides hydroalcoholic extract as well as its ability to repair leukocytes cells to injured tissue. Cissus sicyoides did not demonstrate cytotoxic activity but showed an inhibition of tumor growth in face of the tumors tested. The extract had a strong chemotactic effect on the twenty four hours period after treatment. The hidroalchoolic extract of Cissus sicyoides presented antitumor activity which was prompted by T lymphocytes recruitment to the local lesion and suggests a new pathway to antitumor activity by activation of lymphoid lineage.

Cissus sicyoides pertence à família das Vitaceae. É conhecido popularmente como "insulina, cipó-puca, bejuco caro, puci, anil trepador". Esta planta apresenta efeito vasoconstritor eatividade antibacteriana. No Brasil, C. sicyoides foi avaliado pelas suas propriedades anticonvulsivante e anti-diabética. Estudos fitoquímicos identificaram e isolaram a partir de suas partes aéreas o sitoesterol e o resveratrol compostos que são apontados por apresentar atividade antitumoral. O objetivo deste estudo foi investigar as atividades citotóxica e antitumoral do extrato hidroalcoólico Cissus sicyoides bem como a sua capacidade de recrutar leucócitos para os tecidos lesados. Cissus sicyoides não demonstrou atividade citotóxica, mas apresentou uma inibição do crescimento tumoral frente aos tumores testados. O extrato teve um forte efeito quimiotático 24 h após o tratamento. O extrato hidroalcoólico de Cissus sicyoides apresentou atividade antitumoral, relacionada ao recrutamento de linfócitos T para o local da lesão sugerindo que esta atividade esteve relacionada à ativação da linhagem linfóide.

Produção de IL-10 em resposta a aeroalérgenos em crianças e adolescentes de zona urbana com geohelmintíases / IL-10 production in response to aeroallergens by children and teenage from urban areas with geohelminthiasis

Objetivos: A IL-10 pode imunomodular as respostas alérgicas no hospedeiro. A respeito dos geohelmintos, trabalhos divergem quanto à alteração do quadro clínico e/ou testes cutâneos de hipersensibilidade. Pouco é conhecido sobre a produção de IL-10 frente a aeroalérgenos durante as geohelmintíases. Neste estudo, verificamos a produção de IL-10 por células mononucleares de sangue periférico de pacientes com ou sem geohelmíntiases, de zona urbana, em resposta ao Dermatophagoides pteronyssinus ou Blomia tropicalis. Métodos: Estudo experimental, com 21 pacientes de zona urbana, em que foram realizadas 84 determinações de IL-10. Após exames coprológicos, em triplicata, dois grupos foram formados, crianças enteroparasitadas e não-parasitadas. Amostras de sangue foram coleta das para purificação de células mononucleares e cultivo com antígenos de Ascaris sp (Asc), mitógeno concanavalina A (Con A), O. pteronyssinus (Dep) e B. tropicalis (Bt). A IL-10 do sobrenadante celular foi dosada (ELISA). Resultados: Idade dos pacientes variou de 9-12 anos e sem diferença quanto ao sexo. Nos indivíduos parasitados a carga parasitária foi baixa. Frente ao Asc, Con A ou Dep não houve diferença na síntese de IL-10 pelas células do grupo parasitado e não parasitado. Contudo, uma produção significativamente maior de IL-10, frente ao estímulo com Bt, nos não-parasitados foi observada. Conclusões: Pacientes de zona urbana parasitados produzem menos IL-10 frente à B. tropicalis, alérgeno mais prevalente em Recife, podendo levar a predisposição às manifestações alérgicas. Estes dados corroboram a hipótese que baixa carga parasitária de geohelmintos, principalmente Ascaris lumbricoides, pode predispor à asma/sibilância.

Objectives: IL-10 can immunomodulate allergic reactions in the host. Concerning of the geohelminths, the studies diverge about the alteration of clinical allergic disease and/or skin prick test reactivity. IL-10 production in response to aeroallergens during the geohelminths infection is poorly known. In this study, we verified the IL-10 syntheses by peripheral blood mononuclear cells from low parasitic load infected or non-infected patients coming from urban areas, when stimulated with Dermatophagoides pteronyssinus (Dep) or Blomia tropicalis (Bt). Methods: Experimental analysis of 21 patients from urban areas, which was performed 84 IL-10 determinations. After the parasitological exams (Hofmann/Kato-Katz), in triplicate, two groups were obtained, geohelminths infected and non-infected children. Blood sample were harvested for purification of mononuclear cells and culture with Ascaris sp antigen (Asc), concanavalina A mitogen (Con A), Dep and Bt. IL-10 content in cellular supernatant was measured (ELISA). Results: Patients age was among 9-12 years old and without difference in gender. In parasite infected individual the parasite load was low. In response to Asc, Con A or Dep there was not difference in the IL-10 synthesis. However, in response to Bt stimulus, high production of IL-10 by non-parasite infected group was observed. Conclusions: Parasite infected patients from urban areas product less IL-10 to Bt, allergen more prevalent in Recife, could lead to predisposition to allergic manifestation. These finding corroborate the hypotheses that low parasite load of geohelminths, especially Ascaris lumbricoides, can predispose to asth ma/wheezing.

Preliminary results on interleukin-4 and interleukin-10 cytokine production in malnourished, inducible nitric oxide synthase-deficient mice with schistosomiasis mansoni infection

Schistosoma mansoni infected C57Bl/6 inducible nitric oxide synthase (iNOS)-deficient and non-deficient malnourished mice, both fed a balanced controlled diet were studied. Interleukins, IL-4 and IL-10 responses to soluble egg antigens (SEA) 90 days after infection, were determined. Our results suggest that in iNOS deficient, malnourished mice, 90 days after of infection, nitric oxide has a downregulating effect on IL-4 and IL-10 production. We are currently investigating the biological significance of these findings.

Preliminary results on interleukin-4 and interleukin-10 cytokine production in malnourished, inducible nitric oxide synthase-deficient mice with schistosomiasis mansoni infection.

Schistosoma mansoni infected C57Bl/6 inducible nitric oxide synthase (iNOS)-deficient and non-deficient malnourished mice, both fed a balanced controlled diet were studied. Interleukins, IL-4 and IL-10 responses to soluble egg antigens (SEA) 90 days after infection, were determined. Our results suggest that in iNOS deficient, malnourished mice, 90 days after of infection, nitric oxide has a downregulating effect on IL-4 and IL-10 production. We are currently investigating the biological significance of these findings.

IL-4 and IL-10 are essential for immunosuppression induced by high molecular weight proteins from Ascaris suum.

The extract from Ascaris suum worms (Asc) impairs Th1 and Th2 responses to a non-related antigen, i.e. ovalbumin (OVA). Its suppressive capacity is due to high molecular weight components present in a gel filtration fraction (PI). This fraction is able to elicit IL-4 and IL-10 secretion. Interestingly enough, it induces anti-PI non-anaphylactic IgG1 synthesis through the action of IL-12/IFN-gamma. Here, we investigated the down-regulation of the immune response to OVA by PI in IL-12, IFN-gamma, IL-4 or IL-10 C57BL/6 knockout mice immunized with OVA+PI in adjuvant. OVA-induced delayed-type hypersensitivity (DTH) reactions, secretion of IL-2 and IFN-gamma, and IgG1, IgG2c and IgE antibody production were suppressed by PI in wild-type mice, as well as in IL-12- or IFN-gamma-deficient mice. In contrast, PI had no effect on anti-OVA IgE production and DTH, and induced only a partial suppression of IgG1 and IFN-gamma in IL-10(-/-) mice. The experiments also showed that IL-4 was involved in the PI-induced suppression of IgG2c antibodies and IL-2 secretion. Finally, down-regulation of IFN-gamma was not seen in mice lacking both IL-4 and IL-10, i.e. IL-4(-/-) mice treated with anti-IL-10 antibodies before immunization. These results exclude the participation of IL-12 and IFN-gamma in PI-induced immunosuppression, and highlight the essential role of IL-10 in the suppression of OVA-specific Th2-related parameters, as well as the cooperation between IL-10 and IL-4 in the suppression of Th1-related parameters.