Interleukin-37 Expression Is Increased in Chronic HIV-1-Infected Individuals and Is Associated with Inflammation and the Size of the Total Viral Reservoir.
Jesper F Højen,Thomas A Rasmussen,Karen Lise Dahl Andersen,Anni Winckelmann,Rune R. Laursen,Jesper Damsgaard Gunst,Holger Jon Møller,Mayumi Fujita,Lars Østergaard,Ole S. Søgaard,Charles A. Dinarello,Charles A. Dinarello,Martin Tolstrup +12 more
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TLDR
The data shows that the level of IL-37 mRNA is affected by chronic HIV-1-infection, and a relationship with the activation of the monocyte compartment is suggested by the correlation with sCD14 and, interestingly,IL-37 could be related to the size of the total viral HIV- 1 reservoir.Abstract:
Interleukin-37 (IL-37) is a recently identified cytokine with potent antiinflammatory and immunosuppressive functions. The objective of this study was to compare levels of IL-37 mRNA in immunological subgroups of chronic human immunodeficiency virus-1 (HlV-1)-infected individuals and noninfected controls, to determine IL-37’s association with biomarkers of inflammation and reservoir size. This was a cross-sectional study. The HIV-1-infected patients were categorized in three subgroups depending on their combination antiretroviral therapy (cART) treatment status and CD4+ T-cell count. Quantitative RT-PCR was used for the detection of IL-37 mRNA and HIV-1 DNA in peripheral blood mononuclear cells (PBMCs). Biomarkers in plasma were quantified by enzyme-linked immunosorbent assay (ELISA), whereas T-cell activation was determined by flow cytometry. Lastly, lipopolysaccharide (LPS) stimulations of patients PBMCs were carried out to determine differences in IL-37 mRNA response between the subgroups. Sixty HIV-1-infected patients and 20 noninfected controls were included in the study. Steady-state IL-37 mRNA levels in PBMCs were significantly higher in HIV-1-infected individuals compared with noninfected controls: 2.4-fold (p ≤ 0.01) cART-naive subjects; 3.9-fold (p ≤ 0.0001) inadequate immunological responders; and 4.0-fold (p ≤ 0.0001) in immunological responders compared with noninfected controls. Additionally, levels of the monocyte inflammatory marker sCD14 correlated with IL-37 mRNA (p = 0.03), whereas there was no association with T-cell activation. Finally, we observed a significant correlation between total viral HIV-1 DNA and IL-37 mRNA in PBMCs (p < 0.0001). Collectively, our data shows that the level of IL-37 mRNA is affected by chronic HIV-1-infection. A relationship with the activation of the monocyte compartment is suggested by the correlation with sCD14 and, interestingly, IL-37 could be related to the size of the total viral HIV-1 reservoir.read more
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Overview of the IL-1 family in innate inflammation and acquired immunity.
TL;DR: Although the inflammatory properties of the IL‐1 family dominate in innate immunity, IL‐2 family member can play a role in acquired immunity and this overview is a condensed update.
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Suppression of inflammation and acquired immunity by IL-37
TL;DR: In humans, IL‐37 likely functions to limit excessive inflammation: accordingly,IL‐37 levels are abnormal in patients with inflammatory and autoimmune diseases and the potential for development of this cytokine as a therapeutic agent is discussed.
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Suppression of innate inflammation and immunity by interleukin‐37
Charles A. Dinarello,Charles A. Dinarello,Claudia A. Nold-Petry,Marcel F. Nold,Mayumi Fujita,Suzhao Li,Soo-Hyun Kim,Soo-Hyun Kim,Philip Bufler +8 more
TL;DR: The data reviewed here suggest a therapeutic potential for IL‐37, which binds to the IL‐18 receptor but then recruits the orphan IL‐1R8 (formerly TIR8 or SIGIRR) in order to function as an inhibitor.
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TL;DR: Residual inflammation during ART is likely to be a critical parameter contributing to HIV persistence, and reducing inflammation may be an efficient way to interfere with the maintenance of the HIV reservoir in virally suppressed individuals on ART.
Hospitalization for pneumonia among individuals with and without HIV infection, 1995-2007: a Danish population-based, nationwide cohort study
Ole Schmeltz Søgaard,Nicolai Lohse,Jan Gerstoft,Gitte Kronborg,Lars Østergaard,Court Pedersen,Gitte Pedersen,Henrik Toft Sørensen,Niels Obel +8 more
TL;DR: The risk of pneumonia in people with HIV infection has decreased substantially since the introduction of highly active antiretroviral therapy, but HIV infection remains a strong risk factor for the need for hospitalization to treat pneumonia, even in persons with high CD4(+) cell counts.
References
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