title: Cytokine secretion from brain macrophages infected with human immunodeficiency virus in vitro and treated with raltegravir.
abstract: BACKGROUND
  Integrase inhibitors are a promising class of antiretroviral drugs to treat chronic human immunodeficiency virus (HIV) infection. During HIV infection, macrophages can extravasate from the blood to the brain, while producing chemotaxic proteins and cytokines, which have detrimental effects on central nervous system cells. The main goal of this study was to understand the effects of raltegravir (RAL) on human brain macrophage production of immune-mediators when infected with HIV, but did not compare with other antiretroviral agents.
  
  
  METHODS
  Pro-inflammatory cytokines, IFN-γ, IL-10, IL-12-p70, IL-1, IL-8, TNF-α, and IL-6 were measured simultaneously in tissue culture supernatants from primary brain derived macrophages, microglia. We tested the effects of RAL on markers of astrocytosis and neurite integrity in primary human neuroglial cultures.
  
  
  RESULTS
  RAL administered at 20 nM effectively suppressed HIV infection in microglia over 9 days. Only IL-8, IL-10, and TNF-α were above the detection limit in the majority of samples and RAL significantly suppressed the rate of cytokine production in HIV-infected microglia. During RAL-alone, the rate of IL-8 secretion was higher.
  
  
  CONCLUSIONS
  RAL did not affect neurite area but inhibited astrocyte growth in the neuroglial cultures. Exploring the effects of RAL on pro-inflammatory molecule production in brain macrophages may contribute to designing ARV neuroprotective strategies in chronic HIV infection.
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0603, USA. etatro@ucsd.edu.
authors.forename: Erick T
authors.initials: ET
authors.lastname: Tatro
authors.forename: Benchawanna
authors.initials: B
authors.lastname: Soontornniyomkij
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Cristian L
authors.initials: CL
authors.lastname: Achim
mesh_terms: D001921:Brain / Q000196:embryology / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D015658:HIV Infections / Q000821:virology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000821:virology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000821:virology*; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D011760:Pyrrolidinones; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D000068898:Raltegravir Potassium