title: Distinct cytokine/chemokine network in semen and blood characterize different stages of HIV infection.
abstract: OBJECTIVE
  The cytokine/chemokine network is used by the innate and adaptive immune system to orchestrate effective immune responses. Here, we describe the cross-sectional association between cytokine levels and stage of HIV infection to gain novel insights into HIV-1 immunopathogenesis and identify novel therapeutic targets.
  
  
  METHODS
  Concentrations of 31 cytokine/chemokines were retrospectively measured in blood and seminal plasma collected from 252 individuals enrolled in four well characterized cohorts: HIV-uninfected, untreated HIV-infected in early phase of infection, untreated HIV-infected in late phase of infection, and HIV-infected on antiretroviral therapy with undetectable HIV RNA levels in blood (<50 copies/ml).
  
  
  METHODS
  Cytokine/chemokine levels were measured by multiplex-bead array. Comparisons between groups were performed by Mann-Whitney U-test and P values were adjusted for multiple comparisons using the Benjamini-Hochberg method.
  
  
  RESULTS
  Presence of HIV-infection skewed the cytokine/chemokine network towards a pro-inflammatory response in both blood and semen compared to HIV-uninfected controls. Such changes emerged within the first weeks of infection and were maintained thereafter: Among untreated HIV-infected individuals, none of the 31 measured cytokines were significantly different between early and later stages of infection. Suppression of plasma HIV RNA with ART did not result in normalization of the levels of pro-inflammatory cytokines in blood. In semen, several pro-inflammatory cytokines were even further upregulated in ART-treated compared with HIV-uninfected and HIV-untreated individuals.
  
  
  CONCLUSIONS
  A profound disruption in the cytokine/chemokine network is evident in blood and semen from the earliest stage of HIV infection shortly after the first detection of systemic viremia. These changes are maintained throughout the chronic phase of the infection and do not normalize despite ART and suppression of plasma HIV RNA.
authors.affiliation: aNational Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland bUniversity of California-San Diego, La Jolla cLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance dUniversity of Southern California Keck School of Medicine, Los Angeles eVeterans Affairs San Diego Healthcare System, California fNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. *Christophe Vanpouillea and Andrea Introini contributed equally to the writing of this article. †Andrea Introini is currently at the Department of Medicine, Karolinska Institute Hospital, Solna, Stockholm, Sweden. ‡Andrea Lisco and Sara Gianella contributed equally to the writing of this article.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vanpouille
authors.forename: Andrea
authors.initials: A
authors.lastname: Introini
authors.forename: Sheldon R
authors.initials: SR
authors.lastname: Morris
authors.forename: Leonid
authors.initials: L
authors.lastname: Margolis
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dube
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Little
authors.forename: David M
authors.initials: DM
authors.lastname: Smith
authors.forename: Andrea
authors.initials: A
authors.lastname: Lisco
authors.forename: Sara
authors.initials: S
authors.lastname: Gianella
mesh_terms: D000328:Adult; D001774:Blood Chemical Analysis; D016207:Cytokines / Q000032:analysis* / Q000097:blood; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D007118:Immunoassay; D008297:Male; D012189:Retrospective Studies; D012661:Semen / Q000737:chemistry*
chemical_list: D016207:Cytokines