title: Interleukin-37 Expression Is Increased in Chronic HIV-1-Infected Individuals and Is Associated with Inflammation and the Size of the Total Viral 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 (HIV-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-naïve subjects; 3.9-fold (p ≤ 0.0001) inadequate immunological responders; and 4.0-fold (p ≤ 0.0001) in immunological responders compared with non-infected 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.
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Jesper F
authors: JF
authors: Højen
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Thomas A
authors: TA
authors: Rasmussen
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Karen Lise D
authors: KL
authors: Andersen
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Anni A
authors: AA
authors: Winckelmann
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Rune R
authors: RR
authors: Laursen
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Jesper D
authors: JD
authors: Gunst
authors: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors: Holger J
authors: HJ
authors: Møller
authors: Department of Dermatology, University of Colorado Denver, Aurora, Colorado, United States of America.
authors: Mayumi
authors: M
authors: Fujita
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Lars
authors: L
authors: Østergaard
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Ole S
authors: OS
authors: Søgaard
authors: Division of Infectious Diseases, University of Colorado Denver, Aurora, Colorado, United States of America.|Department of Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors: Charles A
authors: CA
authors: Dinarello
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Martin
authors: M
authors: Tolstrup
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000097:blood / Q000378:metabolism; D019562:Viral Load; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; C508587:IL37 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface