title: Interleukin-15 (IL-15) Strongly Correlates with Increasing HIV-1 Viremia and Markers of Inflammation.
abstract: OBJECTIVE
  IL-15 has been postulated to play an important role in HIV-1 infection, yet there are conflicting reports regarding its expression levels in these patients. We sought to measure the level of IL-15 in a large, well characterised cohort of HIV-1 infected patients and correlate this with well known markers of inflammation, including CRP, D-dimer, sCD163 and sCD14.
  
  
  METHODS
  IL-15 levels were measured in 501 people (460 patients with HIV-1 infection and 41 uninfected controls). The HIV-1 infected patients were divided into 4 groups based on viral load: <50 copies/ml, 51-10,000 copies/ml, 10,001-100,000 copies/ml and >100,000 copies/ml. The Mann Whitney test (non-parametric) was used to identify significant relationships between different patient groups.
  
  
  RESULTS
  IL-15 levels were significantly higher in patients with viral loads >100,000 copies/ml (3.02 ± 1.53 pg/ml) compared to both uninfected controls (1.69 ± 0.37 pg/ml, p<0.001) or patients with a viral load <50 copies/ml (1.59 ± 0.40 pg/ml (p<0.001). There was a significant correlation between HIV-1 viremia and IL-15 levels (Spearman r = 0.54, p<0.001) and between CD4+ T cell counts and IL-15 levels (Spearman r = -0.56, p<0.001).
  
  
  CONCLUSIONS
  IL-15 levels are significantly elevated in HIV-1 infected patients with viral loads >100,000 copies/ml compared to uninfected controls, with a significant direct correlation noted between IL-15 and HIV-1 viremia and an inverse correlation between IL-15 levels and CD4+ T cell counts. These data support a potential role for IL-15 in the pathogenesis of HIV-associated immune activation.
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States of America.|Department of Clinical Immunology, Western Sydney Local Health District, Sydney, Australia.|Sydney Medical School, University of Sydney, Sydney, Australia.|School of Medicine, Western Sydney University, Sydney, Australia.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States of America.
authors.forename: Ju
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States of America.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Rupert
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, 20892, United States of America.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States of America.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Higgins
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States of America.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Dewar
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States of America.
authors.forename: Randy
authors.initials: R
authors.lastname: Stevens
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, United States of America.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Rehm
authors.affiliation: Division of Clinical Research, NIAID, NIH, Bethesda, MD, 20892, United States of America.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Metcalf
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States of America.
authors.forename: Brad T
authors.initials: BT
authors.lastname: Sherman
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States of America.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Baseler
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, United States of America.|Division of Clinical Research, NIAID, NIH, Bethesda, MD, 20892, United States of America.
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States of America.
authors.forename: Tomozumi
authors.initials: T
authors.lastname: Imamichi
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000097:blood* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D019409:Interleukin-15 / Q000097:blood* / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood / Q000276:immunology; D014766:Viremia / Q000097:blood* / Q000276:immunology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D005338:Fibrin Fibrinogen Degradation Products; C569274:IL15 protein, human; D019409:Interleukin-15; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; C036309:fibrin fragment D; D002097:C-Reactive Protein