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J.Immunology:一种新药物或可前进艾滋病医治作用

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Increased activity of IDO, which catalyzes the degradation of Trp into kynurenine (Kyn), is observed during HIV/SIV infection, and it may contribute to the persistence of HIV/SIV by suppressing antiviral T cell responses. We administered the IDO inhibitor 1-methyl-D-tryptophan (D-1mT) for 13 days to SIV-infected rhesus macaques receiving antiretroviral therapy (ART). D-1mT treatment increased the plasma levels of Trp, without reducing the levels of Kyn, suggesting only a partial effect on IDO enzymatic activity. Surprisingly, D-1mT significantly reduced the virus levels in plasma and lymph nodes of ART-treated animals with incomplete responsiveness to ART. In SIV-infected animals that were not receiving ART, D-1mT was ineffective in reducing the plasma viral load and had only a marginal effect on the plasma Kyn/Trp ratio. Increased IDO and TGF-β mRNA expression in lymph nodes of ART-treated macaques after D-1mT treatment suggested that compensatory counterregulatory mechanisms were activated by D-1mT, which may account for the lack of effect on plasma Kyn. Finally, D-1mT did not interfere with the ART-induced T cell dynamics in lymph nodes (increased frequency of total CD4 T cells, increase of CD8 T cell****pressing the antiapoptotic molecule Bcl2, and reduction of regulatory T cells). Thus, D-1mT appeared to synergize with ART in inhibiting viral replication and did not interfere with the beneficial immunologic effects of ART. Further studies are required to elucidate the immunologic or virologic mechanism by which D-1mT inhibited SIV replication in vivo.

现在,医治艾滋病一般运用高效抗逆转录病毒疗法,俗称鸡尾酒疗法,但约有非常之一的艾滋病病毒感染者因为抗药性等要素,这种疗法对他们没有作用。因此研究人员期望他们的新研究未来能前进鸡尾酒疗法的作用。

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3 Address correspondence and reprint requests to Dr. Adriano Boasso, Imperial College, Faculty of Medicine, Department of Immunology, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, U.K.

其他,动物测验还证明,只运用D-1mT医治感染SIV的猕猴并没有作用。研究人员暗示,下一步他们将研究D-1mT是怎么阐扬效果的。


6 Abbreviations used in this *****: ART, antiretroviral therapy; D-1mT, 1-methyl-D-tryptophan; Kyn, kynurenine; Neo, neopterin; Treg, regulatory T cell.

英国帝国理工学院等组织的研究人员4月1日在《免疫学杂志》(The Journal of Immunology)上说,他们把一种名为D-1mT的氨基酸药物与抗逆转录病毒疗法联合运用,明显降低了猕猴体内的猿类免疫缺点病毒SIV的程度。SIV是迄今已知与人类艾滋病病毒最接近的病毒。

2 A.B. and M.V. contributed equally to this work.

J.Immunology:一种新药物或可进步艾滋病医治作用

Combined Effect of Antiretroviral Therapy and Blockade of IDO in SIV-Infected Rhesus Macaques1

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

4 Current address: Vitae Pharmaceuticals, Ft. Washington, PA 19034.

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7 The online version of this article contains supplemental material.

The Journal of Immunology, 2009, 182: 4313-4320

Adriano Boasso2,3,*,, Monica Vaccari2,, Dietmar Fuchs, Andrew W. Hardy4,*, Wen-Po Tsai, Elzbieta Tryniszewska5,, Gene M. Shearer* and Genoveffa Franchini

1 This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (to A.B., M.V., A.W.D., W.P.T., E.T., G.M.S., and G.F.), and by the government of the State of the Austrian Tyrol (to D.F.).
一项新研究显现,那些用抗逆转录病毒疗法医治没有作用的艾滋病病毒感染者,未来再联合用一种氨基酸药物中止医治,或许能够明显改进他们的保存状况。

关键词:药物,艾滋病

* Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;   Immunology Department, Imperial College, Chelsea and Westminster Hospital, London, U.K.;   Animal Models and Retroviral Vaccines Section, National Cancer Institute, National Institutes of Health, Bethesda MD 20892; and   Division of Biological Chemistry Biocentre, Innsbruck Medical University, Innsbruck, Austria

现在,一些研究小组正在中止初阶临床实验验证D-1mT医治癌症的慈祥性和效果。研究人员指出,假设实验证明D-1mT能慈祥运用于人体,大约他们最早将于5年内开始实施D-1mT医治艾滋病的临床实验。(生物谷Bioon.com)

J.Immunology:一种新药物或可进步艾滋病医治作用

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研究人员接着让这8只猕猴每天服用必定剂量的D-1mT,并在第6天和第13地利遭受血液检测,效果发现,第6地利只剩下3只猕猴体内SIV含量仍处于可测程度,第13地利只剩下2只猕猴体内SIV含量处于可测程度,且含量非常低。

研究人员在测验中共运用了11只感染SIV的猕猴,它们先遭受鸡尾酒疗法,阶段至少4个月,效果此中只需3只体内的SIV降到不成测的程度,另8只则不见作用,SIV依然坚持较高程度。

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5 Current address: Department of Microbiology Diagnostics, Medical University of Bialystok, Bialystok, Poland.