Schistosoma mansoni infection or associated products are able to down-modulate the type 1 CD4+ T cell inflammatory response characteristic of autoimmune diseases. In this study, we evaluated how S. mansoni antigens altered the immune response that was induced by the soluble Leishmania antigen (SLA) from cutaneous leishmaniasis (CL) patients. Cytokines were measured from the supernatants of peripheral blood mononuclear cell cultures stimulated with SLA. This was performed using the sandwich enzyme linked immunosorbent assay technique in the presence or absence of S. mansoni recombinant antigens Sm29, SmTSP-2 and PIII. The addition of S. mansoni antigens to the cultures resulted in the reduction of interferon gamma (IFN-γ) levels in 37-50% of patients. Although to a lesser extent, the antigens were also able to decrease the production of tumour necrosis factor-alpha (TNF-α). We compared patients that either had or did not have reduction in IFN-γ and TNF-α production in cultures stimulated with SLA in the presence of S. mansoni antigens. We found that there was no significant difference in the levels of interleukin (IL)-10 and IL-5 in response to S. mansoni antigens between the groups. The antigens used in this study down-modulated the in vitro proinflammatory response induced by SLA in a group of CL patients through a currently undefined mechanism.

OBJETIVO: Revisão crítica da literatura sobre a associação entre asma e diabetes mellitus tipo 1 (DM1). FONTE DOS DADOS: Pesquisa bibliográfica na base de dados MEDLINE e LILACS nos últimos vinte anos. SÍNTESE DOS DADOS: Muitos estudos mostram associação inversa entre asma, atopia e o risco de desenvolver DM1. De acordo com a "Hipótese da Higiene", o risco de doenças alérgicas diminui com infecções precoces na infância no sentido de afastar-se do perfil Th2, predominante ao nascimento, em direção ao fenótipo Th1. No entanto, outros trabalhos demonstram associação positiva ou ausência de associação entre DM1 e alergias. Existe a possibilidade de fatores ambientais contribuírem para ocorrência de doenças mediadas por células Th1 e Th2 no mesmo indivíduo, por provável deficiência de mecanismos imunomodulatórios mediados pela interleucina-10 e células regulatórias. CONCLUSÃO: As informações sobre a associação inversa entre doenças mediadas por resposta Th1 (por exemplo, DM1), e aquelas mediadas por resposta Th2 (por exemplo, alergias) são conflitantes, requerendo mais estudos para esclarecer esta questão.

OBJECTIVE: Critical review of the literature to investigate the relationship between asthma and type 1 diabetes mellitus (DM1). SOURCE OF DATA: Bibliography search in MEDLINE and LILACS databases in the last twenty years. SUMMARY OF DATA: Several studies demonstrate an inverse relationship between asthma, atopic diseases and the risk to develop DM1. According to the "Hygiene Hypothesis", the risk of allergic diseases decreases with infections early in childhood, towards distance of Th2 profile, common at birth, to the Th1 phenotype. Other articles described lack of association or positive association between DM1 and allergies. There is a possibility of environmental factors interfering in the development of disorders mediated by Th1 and Th2 cells, in the same individual, due to the absence of immunomodulatory mechanisms mediated by interleukin-10 and regulatory cells. CONCLUSION: The existing information about the inverse association between Th1-mediated diseases (e.g., DM1), and those that are Th2-mediated (e.g., allergies) are conflicting requiring more investigation to explain this question.

INTRODUÇÃO: o HTLV-1 é um retrovírus humano associado à leucemia de células T do adulto e à mielopatia associada ao HTLV-1 ou paraparesia espástica tropical, que tem sido implicado também no desenvolvimento de auto-imunidade. OBJETIVO: o objetivo deste estudo foi determinar a freqüência de doenças reumáticas auto-imunes em pacientes infectados pelo HTLV-1. PACIENTES E MÉTODOS: foram incluídos nesse estudo 137 indivíduos infectados pelo HTLV-1 atendidos no Ambulatório Multidisciplinar do Serviço de Imunologia do Hospital Universitário Professor Edgard Santos (HUPES) da Universidade Federal da Bahia (UFBA), no período de janeiro de 2003 a maio de 2004. Os pacientes responderam a um questionário geral relacionado a manifestações reumatológicas e questionários específicos para confirmação dos critérios diagnósticos de artrite reumatóide (AR), lúpus eritematoso sistêmico (LES), síndrome de Sjögren e polimiosite. Adicionalmente, todos eles foram submetidos a exames clínicos específicos e avaliação complementar. RESUTADOS: 24 pacientes tiveram o diagnóstico de síndrome de Sjögren (SS) provável (17,5%), 18 pacientes (13,1%) de AR, uma paciente teve diagnóstico de LES e uma de doença mista do tecido conjuntivo (0,7%, respectivamente). Suspeita de artropatia relacionada ao vírus foi encontrada em 22 pacientes (16,1%). Síndrome de Sjögren e AR foram mais freqüentes nos pacientes com mielopatia (33,3 e 25,9%, respectivamente) do que nos portadores assintomáticos (13,6 e 10%, respectivamente). Artropatia relacionada ao HTLV-1 ocorreu com freqüência semelhante em ambos os grupos. CONCLUSÃO: foi observado neste trabalho alta prevalência de síndrome de Sjögren e de AR entre os indivíduos infectados pelo HTLV-1, principalmente naqueles com mielopatia. Diante desses resultados, que reforçam os dados da literatura, deve-se estar atento para a ocorrência de doenças reumáticas auto-imunes nesses pacientes.

INTRODUCTION: the HTLV-1 is a human retrovirus associated with adult T-cell leukaemia (ATL) and with HTLV-1- associated myelopathy or tropical spastic paraparesis, which has also been implicated in the development of autoimmunity. OBJECTIVE: the aim of this study was to determine the frequency of autoimmune rheumatic diseases in patients infected with HTLV-1. PATIENTS AND METHODS: it was included 137 individuals infected with HTLV-1 from the Multidisciplinary Ambulatory of Immunology Service, HUPES-UFBA, Salvador (BA), from January 2003 to May 2004. All participants answered to a general questionnaire regarding rheumathological manifestations and specific questionnaires to confirm the diagnose criteria of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS) and polymyositis. Additionally, they were submitted to specific clinical exams, besides complementary evaluations. RESULTS: 24 patients had diagnose of probable Sjögren’s syndrome (17.5%), 18 patients (13.1%) had RA, one patient had diagnose of SLE (0.7%) and another of mixed connective tissue disease (0.7%, respectively). HTLV-1-associated arthropathy (HAAP) was suspected in 22 individuals (16.1%). Sjögren’s syndrome and RA were more frequent in patients with myelopathy (33.3 and 25.9%, respectively) than in asymptomatic carriers (13.6 and 10%, respectively). The frequency of HTLV-1-associated arthropathy was the same in both groups. CONCLUSION: in this study it was observed a high frequency of Sjögren’s syndrome and RA in individuals infected with HTLV-1, mainly in those with myelopathy. Therefore, with this results that support data in the literature, we should call attention to the occurrence of autoimmune rheumatic diseases in these kind of patients.

O HTLV-1 foi o primeiro retrovírus humano a ser associado às doenças malignas leucemia e linfoma de células T do adulto (LLTA). Ele está relacionado também a uma doença inflamatória crônica do sistema nervoso central (SNC) conhecida como paraparesia espástica tropical/mielopatia associada ao HTLV-1 (PET/MAH). O HTLV-1 tem sido implicado na patogênese de várias doenças auto-imunes, tais como: diabetes, esclerose múltipla, dermatite infectiva, uveíte e artropatia. Ao longo dos anos, a infecção retroviral tem assumido um importante papel na patogênese das doenças reumáticas auto-imunes. Partículas semelhantes aos retrovírus têm sido identificadas em tecidos de pacientes com artrite reumatóide (AR), síndrome de Sjögren, lúpus eritematoso sistêmico (LES) e polimiosite. A síndrome de Sjögren e a AR têm sido as doenças reumáticas mais encontradas nos pacientes infectados pelo HTLV-1, sendo a freqüência mais elevada nos pacientes com mielopatia. A alta prevalência de síndrome de Sjögren e de AR entre os indivíduos com mielopatia sugere que a carga viral e a resposta inflamatória exacerbada, que concorrem para o desenvolvimento da mielopatia, devem também influenciar no desenvolvimento das doenças reumáticas auto-imunes.

The HTLV-1 was the first human retrovirus associated with adult T-cell leukemia/lymphoma (LLTA). The virus also causes a chronic inflammatory disease of the central nervous system named HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP). HTLV-1 has been implicated in the pathogenesis of many autoimmune diseases, such as diabetes, multiple sclerosis, infective dermatitis, uveitis and arthropathy. It has long been suggested that retroviral infection may play a role in the pathogenesis of autoimmune rheumatic diseases. Particles resembling retroviruses have been reported in tissue from patients with rheumatoid arthritis (RA), Sjögren’s syndrome, systemic lupus erythematosus (SLE) and polymyositis. Sjögren’s syndrome and RA have been the most frequent rheumatic diseases in patients infected with HTLV-1, being more prevalent in patients with myelopathy. The high prevalence of Sjögren’s syndrome and RA in individuals with myelopathy, suggests that the viral burden and exacerbated inflammatory response may play a role not only in the development of myelopathy, but may also influence the outcome of autoimmune rheumatic diseases.

The need to develop a vaccine against schistosomiasis led several researches and our group to investigate proteins from Schistosoma mansoni as vaccine candidates. Sm22.6 is a protein from S. mansoni that shows high identity with Sj22.6 and Sh22.6 (79 and 91%, respectively). These proteins are associated with high levels of IgE and protection to reinfection. Previously, we have shown that Sm22.6 induced a partial protection of 34.5% when used together with Freund's adjuvant and produced a Th0 type of immune response with interferon-g and interleukin-4. In this work, mice were immunized with Sm22.6 alone or with aluminum hydroxide adjuvant and high levels of IgG, IgG1, and IgG2a were measured. Unfortunately, no protection was detected. Since IL-10 is a modulating cytokine in schistosomiasis, we also observed a high level of this molecule in splenocytes of vaccinated mice. In conclusion, we did not observe the adjuvant effect of aluminum hydroxide associated with rSm22.6 in protective immunity.

Asthmatics infected with Schistosoma mansoni have a less severe course of asthma and an inhibition of the Th2 inflammatory response that seems to be mediated by interleukin (IL-10). The objective of this study was to evaluate the capacity of some S. mansoni antigens to stimulate IL-10 production in vitro by cells of asthmatic infected individuals. Peripheral bloods mononuclear cells were stimulated with the S. mansoni recombinant antigens Sm22.6, Sm14, P24, and PIII antigen. IL-10 was measured in the supernatants of cultures. As the recombinant antigens were cloned in Escherichia coli, we blocked contaminant endotoxin with polymyxin B added to the cultures. We demonstrated that all antigens used drove high production of IL-10 in S. mansoni infected individuals (n = 13, 408 ± 514 and 401 ± 383 pg/ml, 484 ± 245 pg/ml, 579 ± 468 pg/ml, respectively). In asthmatics infected with S. mansoni (n = 21) rP24 induced higher levels of IL-10 (565 ± 377 pg/ml) when compared to PIII, rSm14 and rSm22.6 (184 ± 209 pg/ml; 292 ± 243 pg/ml; 156 ± 247 pg/ml, respectively). Conclusion: the S. mansoni antigens evaluated in this study stimulated IL-10 production by cells from infected individuals and therefore they have the potential to be used as a modulator of the inflammatory response in asthma.

O conhecimento dos principais mecanismos de defesa imune contra os diversos agentes infecciosos permite a compreensão da patogênese das doenças infectoparasitárias e das várias estratégias do hospedeiro e do parasita. O sistema imunológico atua numa rede de cooperação, envolvendo a participação de muitos componentes estruturais, moleculares e celulares. Nesse cenário encontra-se o delicado equilíbrio entre a saúde e a doença, em que tanto a deficiência quanto o exagero resultam em dano tecidual. Este artigo explora esses aspectos e algumas abordagens terapêuticas que surgem desse entendimento.

Knowledge acquired about the main immune mechanisms protecting against various infectious agents leads to a better understanding of the pathogenesis of infectious/parasitic diseases and of various strategies specific to the host and parasite. The immune system performs along a cooperation network, which involves the participation of several structural, molecular and cellular components. The fine balance between health and disease is found in this scenario, in which deficiency as much as excess may result in tissue damage. This article explores such aspects and a number of therapies arising from the knowledge acquired.

Chronic Schistosoma mansoni infection leads to a type 2-immune response with increased production of interleukin (IL-10). Evidence indicates chronic exposure to S. mansoni down regulates the type 1 immune response and prevents the onset of Th1-mediated diseases such as multiple sclerosis, diabetes mellitus and Cronh's disease. Furthermore, our own studies have revealed that chronic exposure to S. mansoni also down regulates atopic disease, Th2-mediated diseases. Our studies show an inverse association between the skin prick test reactivity and infection with S. mansoni and show the severity of asthma is reduced in subjects living in an endemic area of S. mansoni. Moreover, we hypothesize the mechanisms involved in the modulation of inflammatory response in atopic individuals, is likely dependent on IL-10 production, an anti-inflammatory cytokine elevated during helminth infections. Patients with asthma and helminth infections produced less IL-5 than patients with asthma without helminth infections, and this down regulation could, in part, be mediated by IL-10. In conclusion, helminthic infections, through induction of regulatory mechanisms, such as IL-10 production, are able to modulate the inflammatory immune response involved in the pathology of auto-immune and allergic disease.

This study objective was to evaluate the cytokines associated with early events of hepatic fibrosis in schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography in 94 patients. Immunological evaluation was performed by measurement of secreted cytokines (interleukin IL-5, IL-10, IL-13, interferon-gamma, tumor necrosis factor-alpha and transforming growth factors-beta) in peripherl blood mononuclear cells stimulated by Schistosoma mansoni antigens. Significantly, higher levels of IL-5, IL-10 and IL-13 were found in supernatants of SEA-stimulated PBMC from subjects with degree III hepatic fibrosis as compared to patients with degree I or II fibrosis, Significant increases in IL-5 and IL-13 levels were also observed in some of the subjects who remained untreated for one year following initial assessment and developed more serious fibrosis during this period. The data suggests a role for type 2 cytokines in early stages of hepatic fibrosis in human schistosomiasis mansoni.

O teste de Montenegro, utilizado no diagnóstico da leishmaniose tegumentar, tem sido recentemente considerado marcador de imunogenicidade após vacinação. Neste estudo, avaliou-se o poder sensibilizante deste teste e a produção de y-IFN in vitro, em indivíduos não expostos a Leishmania. Utilizaram-se para o teste antígenos de L. amazonensis produzido em nosso laboratório (grupo I) ou produzido pela FIOCRUZ-RJ (grupo II). No dia 30, 33% dos indivíduos do grupo I e 42% do grupo II converteram o teste para positivo, comparando-se com 67% do grupo I e 50% do grupo II no dia 90. y-IFN foi detectado em 56% dos indivíduos do grupo I e 17% do grupo II no dia 30 (169±309 e 11±36pg/ml) e em 67% do grupo I e 58% do grupo II no dia 360 (69±107 e 18±20pg/ml). Estes dados demonstram que o teste de Montenegro induz, além de hipersensibilidade tardia, a produção de y-IFN.

The Montenegro skin test, used to diagnose cutaneous leishmaniasis, is now being considered to detect immunogenicity after vaccination. In this study, we evaluated the ability of this test to induce immune response and IFN-g production in subjects not previously exposed to Leishmania. The Montenegro skin test was performed using antigens of L. amazonensis produced by our laboratory (group I) or by FIOCRU-RJ (group II). At day 30, 33% of the subjects from group I and 42% from group II were positive, compared to 67% from group I and 50% from group II at day 90. IFN-y was detected in 56 % of subjects from group I and 17% from group II at day 30 (169±309 and 11±36pg/ml) and in 67% from group I and 58% from group II by day 360 (69±107 and 18±20pg/ml). These data demonstrate that the Montenegro skin test induces not only a delayed hypersensitivity reaction, but also IFN-y production.