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      Reduction of soluble CD163, substance P, programmed death 1 and inflammatory markers: phase 1B trial of aprepitant in HIV-1-infected adults.

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          Abstract

          We evaluated safety, antiviral, immunomodulatory and anti-inflammatory properties of aprepitant - a neurokinin 1 receptor antagonist.

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          Most cited references42

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          The PD-1-PD-L pathway in immunological tolerance.

          Since the first observation of spontaneous autoimmune diseases in programmed cell death 1 (PD-1) knockout mice, PD-1 has been postulated to have essential roles in the regulation of autoimmunity but the precise mechanism was largely unknown. Recent studies clearly demonstrated that PD-1 has dual roles in immunological tolerance: induction and maintenance of peripheral tolerance. PD-1 ligands (PD-Ls) on antigen-presenting cells have been shown to switch off autoreactive T cells and induce peripheral tolerance, whereas those on parenchymal cells prevent tissue destruction by suppressing effector T cells to maintain tolerance. In addition, PD-1 and other immuno-inhibitory receptors have been shown to collaborate in the regulation of tolerance. Here, we review recent studies on the role of PD-1 in immunological tolerance and discuss possible clinical applications of PD-1 manipulation.
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            Redefining the viral reservoirs that prevent HIV-1 eradication.

            This Perspective proposes definitions for key terms in the field of HIV-1 latency and eradication. In the context of eradication, a reservoir is a cell type that allows persistence of replication-competent HIV-1 on a timescale of years in patients on optimal antiretroviral therapy. Reservoirs act as a barrier to eradication in the patient population in which cure attempts will likely be made. Halting viral replication is essential to eradication, and definitions and criteria for assessing whether this goal has been achieved are proposed. The cell types that may serve as reservoirs for HIV-1 are discussed. Currently, only latently infected resting CD4(+) T cells fit the proposed definition of a reservoir, and more evidence is necessary to demonstrate that other cell types, including hematopoietic stem cells and macrophages, fit this definition. Further research is urgently required on potential reservoirs in the gut-associated lymphoid tissue and the central nervous system. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Soluble CD163.

              J Möller (2012)
              CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163) at 0.7-3.9 mg/l in healthy individuals. The function of sCD163 is unknown, but during inflammation and macrophage activation, sCD163 levels increase acutely due to metalloproteinase-mediated cleavage near the cell membrane. It is now evident that sCD163 is very useful as a biomarker of macrophage activation in various inflammatory diseases, such as macrophage activation syndrome, sepsis, and liver disease. Moreover, sCD163 is a general risk marker of comorbidity and mortality in several chronic inflammatory disease states. Recently, sCD163 has been shown to be strongly associated with later development of type 2 diabetes in both lean and obese subjects, likely due to macrophage infiltration of adipose tissue and the liver. This review summarizes the current knowledge on the regulation of sCD163 in normal and pathological states and also deals with analytical aspects of sCD163 measurements in biological samples.
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                Author and article information

                Journal
                AIDS
                AIDS (London, England)
                Ovid Technologies (Wolters Kluwer Health)
                1473-5571
                0269-9370
                May 15 2015
                : 29
                : 8
                Affiliations
                [1 ] aDepartment of Medicine bDepartment of Pediatrics cDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania dThe Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania eWestat, Rockville, Maryland, USA.
                Article
                00002030-201505150-00008
                10.1097/QAD.0000000000000638
                4472318
                25915168
                113f4466-5f0b-477c-bf0c-1143af7df29e
                History

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