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.

Low transformation growth factor-ß1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni.

Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers' fibrosis in humans. In this report, the effects of the host's nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-ß1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-ß1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

Influence of neurotoxoplasmosis characteristics on real-time PCR sensitivity among AIDS patients in Brazil.

Cerebral toxoplasmosis among individuals with AIDS may be difficult to diagnose and needs to be differentiated from other neurological diseases. A validation study was performed on real-time PCR for detecting the B1 gene of Toxoplasma gondii in the blood and cerebrospinal fluid (CSF) of AIDS patients with cerebral toxoplasmosis. The study included 135 AIDS patients divided into two groups: Group I comprised 85 patients with neurotoxoplasmosis; and Group II comprised 50 patients with non-toxoplasmic neurological diseases. Real-time PCR on blood showed a sensitivity of 1.5%, specificity of 100.0%, positive predictive value (PPV) of 100.0% and negative predictive value (NPV) of 36.5%. CSF testing produced better results, with a sensitivity of 35.3%, specificity of 100.0%, PPV of 100.0% and NPV of 44.7%. The group presenting with pleocytosis and four or more encephalic lesions was associated with greater CSF positivity on PCR. In conclusion, real-time PCR on blood was not useful for diagnosis. CSF testing showed low sensitivity but high specificity. Greater numbers of lesions and greater CSF cellularity may improve the sensitivity of the method.

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.

Type I IFNs stimulate nitric oxide production and resistance to Trypanosoma cruzi infection.

The participation of type I IFNs (IFN-I) in NO production and resistance to Trypanosoma cruzi infection was investigated. Adherent cells obtained from the peritoneal cavity of mice infected by the i.p. route produced NO and IFN-I. Synthesis of NO by these cells was partially inhibited by treatment with anti-IFN-alphabeta or anti-TNF-alpha Abs. Compared with susceptible BALB/c mice, peritoneal cells from parasite-infected resistant C57BL/6 mice produced more NO (2-fold), IFN-I (10-fold), and TNF-alpha (3.5-fold). Later in the infection, IFN-I levels measured in spleen cell (SC) cultures from 8-day infected mice were greater in C57BL/6 than in infected BALB/c mice, and treatment of the cultures with anti-IFN-alphabeta Ab reduced NO production. IFN-gamma or IL-10 production by SCs was not different between the two mouse strains; IL-4 was not detectable. Treatment of C57BL/6 mice with IFN-I reduced parasitemia levels in the acute phase of infection. Mice deprived of the IFN-alphabetaR gene developed 3-fold higher parasitemia levels in the acute phase in comparison with control 129Sv mice. Production of NO by peritoneal macrophages and SCs was reduced in mice that lacked signaling by IFN-alphabeta, whereas parasitism of macrophages was heavier than in control wild-type mice. We conclude that IFN-I costimulate NO synthesis early in T. cruzi infection, which contributes to a better control of the parasitemia in resistant mice.

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.