Cytokine Profile and Immunomodulation in Asymptomatic Human T-Lymphotropic Virus Type 1–Infected Blood Donors

Carvalho, Edgar M.; Bacellar, Olı́via; Porto, Aurélia F.; Braga, Silvane; Galvão–Castro, Bernardo; Neva, Franklin A.

doi:10.1097/00126334-200105010-00001

Cited by 84 publications

(81 citation statements)

References 18 publications

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“…Moreover, expression of IL-10 is elevated not only in patients with higher susceptibility to B-cell lymphoma as a result of HIV or hepatitis C virus infection 43,44 but also in asymptomatic HTLV-1 carriers and patients with T-cell lymphomas. [45][46][47] Taken together, our results suggest that deregulation of IL-10 by both functional loss of p53 and lack of iNOS activity plays an important role in nonthymic lymphomagenesis.…”

Section: Discussionsupporting

confidence: 55%

Suppression of thymic lymphomas and increased nonthymic lymphomagenesis in Trp53‐deficient mice lacking inducible nitric oxide synthase gene

Tatemichi

Tazawa

Masuda

et al. 2004

Intl Journal of Cancer

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Trp53-deficient mice spontaneously develop lymphomas, mainly of thymic origin, although the molecular mechanism remains largely unknown. As several interaction effects between p53 and iNOS have been reported, we hypothesized that iNOS activity in the thymus is causally linked to lymphomagenesis in Trp53-deficient mice. We therefore created mouse strains with different combinations of the Trp53 and iNOS genes. Western blot and histologic analyses showed that the iNOS protein was constitutively expressed in the thymus independently of Trp53 status and its expression was enhanced in Trp53 ؉/-and Trp53 -/-mice compared to Trp53 ؉/؉ mice. Homozygous disruption of iNOS decreased the incidence of thymic lymphomas by almost 40% (p ‫؍‬ 0.087) and 90% (p < 0.05) in Trp53 -/-and Trp53 ؉/-mice, respectively, compared to the respective iNOS wild-type mice but significantly (p < 0.05) increased the development of nonthymic lymphomas in Trp53 -/-and Trp53 ؉/-mice. Although iNOS gene disruption did not affect the phenotype of thymic lymphomas, absence of the iNOS gene shifted the spectrum of nonthymic lymphoma from the B-cell to the T-cell lineage. RT-PCR analysis revealed enhanced expression of IL-10, which could have a promoting effect on lymphomagenesis, even without any stimulation, in the spleen of aging mice with the gene combinations Trp53 -/-iNOS -/-and Trp53 ؉/-iNOS -/-but not Trp53 -/-iNOS ؉/؉ or Trp53 ؉/-iNOS ؉/؉ . These results suggest that iNOS could increase the development of thymic lymphomas in Trp53-deficient mice. While iNOS may have protective effects against nonthymic lymphomagenesis, the regulation of cytokine production by iNOS may be involved in the underlying mechanism of antilymphomagenesis effects in the peripheral lymphoid organ.

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Section: Discussionsupporting

confidence: 55%

Suppression of thymic lymphomas and increased nonthymic lymphomagenesis in Trp53‐deficient mice lacking inducible nitric oxide synthase gene

Tatemichi

Tazawa

Masuda

et al. 2004

Intl Journal of Cancer

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“…Em nenhum dos pacientes avaliados foram identificadas manifestações extra-articulares da doença, a exemplo de nódulos subcutâneos. Isso pode sugerir que a doença tenha menor gravidade quando associada ao HTLV-1, embora não seja o esperado, desde que a resposta induzida pelo vírus seja predominantemente do tipo Th1 (8,31) , e a patogênese da AR envolve também a resposta Th1 com alta produção de TNF- (32) , o que, juntos, contribuiriam para a maior gravidade da AR. O fato de a AR ter sido mais freqüente nos pacientes com mielopatia reforça a idéia de que os mediadores inflamatórios que levam ao aparecimento da mielopatia também contribuem para o desenvolvimento da AR.…”

Section: Discussionunclassified

“…Diversos estudos têm demonstrado que o HTLV-1 induz no sistema imune uma resposta proliferativa linfocitária exuberante e, mais recentemente, que células de portadores desse vírus secretam altos níveis de IFN-, TNF-, IL-5 e IL-10 in vitro, na ausência de estímulo, comparados com células de doadores de sangue soronegativos para o HTLV-1 (8) . Desta forma, o HTLV-1 tem sido implicado na indução de auto-imunidade e assim justificando a maior freqüência de doenças reumáticas auto-imunes nesses pacientes.…”

Section: Introductionunclassified

Freqüência de doenças reumáticas em indivíduos infectados pelo HTLV-1

Carvalho¹,

Giozza²,

Santos³

et al. 2006

Rev. Bras. Reumatol.

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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 autoimunes em pacientes infectados pelo HTLV-1. Pacientes e Méto-dos: 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. Resultados: 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.Palavras-chave: HTLV-1, doenças difusas do tecido conjuntivo, doenças reumáticas auto-imunes.

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“…Altered cytokine profiles have been reported in healthy human HTLV carriers, including increased expression of IFN-γ , TNF-α, IL-1α, and IL-6 (2,22,56). Altered cytokine profiles have also been observed in STLV-infection of nonhuman primates.…”

Section: Simian T-lymphotropic Virusmentioning

confidence: 99%

Simian Retrovirus Infections: Potential Confounding Variables in Primate Toxicology Studies

Lerche

Osborn

2003

Toxicol Pathol

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Various species of nonhuman primates are natural hosts for 6 exogenous retroviruses, including gibbon-ape leukemia virus (GaLV), simian sarcoma virus, simian T-lymphotropic virus (STLV), simian immunodeficiency virus (SIV), simian type D retrovirus (SRV), and simian foamy virus (SFV). These viruses establish persistent infections with a broad spectrum of pathogenic potential, ranging from highly pathogenic to nonpathogenic, depending on various host, virus, and environmental factors. Latent or subclinical infections are common, and various procedures associated with experimental protocols may lead to virus reactivation and disease. Adverse effects on toxicologic research by undetected retroviral infections can occur in several ways, including loss of experimental subjects (and statistical power) due to increased morbidity and mortality. In addition, results may be confounded by virus-induced clinical abnormalities, histologic lesions, alteration of physiologic parameters and responses, and interference with in vitro assays and/or destruction of primary cell cultures. Key clinical and epidemiological features of several important retroviruses are reviewed, with emphasis on viruses infecting species of macaques most commonly used as research subjects in primate toxicology studies. Examples of actual and potential confounding of toxicologic studies by retroviruses are discussed, including altered cytokine profiles in healthy STLV carriers, and clinical and pathological abnormalities induced by SRV infection. Adequate prestudy viral screening is critical to exclude retrovirus-infected primates from toxicologic research protocols and prevent potential confounding of research results.

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Cytokine Profile and Immunomodulation in Asymptomatic Human T-Lymphotropic Virus Type 1–Infected Blood Donors

Cited by 84 publications

References 18 publications

Suppression of thymic lymphomas and increased nonthymic lymphomagenesis in Trp53‐deficient mice lacking inducible nitric oxide synthase gene

Suppression of thymic lymphomas and increased nonthymic lymphomagenesis in Trp53‐deficient mice lacking inducible nitric oxide synthase gene

Freqüência de doenças reumáticas em indivíduos infectados pelo HTLV-1

Simian Retrovirus Infections: Potential Confounding Variables in Primate Toxicology Studies

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