Interleukin-15 (IL-15) Strongly Correlates with Increasing HIV-1 Viremia and Markers of Inflammation

PLoS One. 2016 Nov 23;11(11):e0167091. doi: 10.1371/journal.pone.0167091. eCollection 2016.

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.

Design and 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Antigens, CD / blood
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / blood
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Biomarkers / blood
  • C-Reactive Protein / immunology
  • C-Reactive Protein / metabolism
  • CD4 Lymphocyte Count
  • Female
  • Fibrin Fibrinogen Degradation Products / immunology
  • Fibrin Fibrinogen Degradation Products / metabolism
  • HIV Infections / blood*
  • HIV Infections / immunology
  • HIV-1 / immunology
  • HIV-1 / metabolism*
  • Humans
  • Inflammation / blood
  • Inflammation / immunology
  • Interleukin-15 / blood*
  • Interleukin-15 / immunology
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharide Receptors / immunology
  • Male
  • Middle Aged
  • Receptors, Cell Surface / blood
  • Receptors, Cell Surface / immunology
  • Viremia / blood*
  • Viremia / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • Fibrin Fibrinogen Degradation Products
  • IL15 protein, human
  • Interleukin-15
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface
  • fibrin fragment D
  • C-Reactive Protein