Cytokine secretion from brain macrophages infected with human immunodeficiency virus in vitro and treated with raltegravir.
Title | Cytokine secretion from brain macrophages infected with human immunodeficiency virus in vitro and treated with raltegravir. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Tatro, ET, Soontornniyomkij, B, Letendre, SL, Achim, CL |
Journal | BMC Infect Dis |
Volume | 14 |
Pagination | 386 |
Date Published | 2014 Jul 11 |
ISSN | 1471-2334 |
Keywords | Brain, Cytokines, HIV Infections, Humans, Interleukin-10, Interleukin-12, Interleukin-6, Interleukin-8, Internal, Macrophages, Microglia, Pyrrolidinones, Raltegravir Potassium, Tumor Necrosis Factor-alpha |
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. |
DOI | 10.1186/1471-2334-14-386 |
Alternate Journal | BMC Infect Dis |
PubMed ID | 25015002 |
PubMed Central ID | PMC4227040 |
Grant List | P50 DA026306 / DA / NIDA NIH HHS / United States R03DA033849 / DA / NIDA NIH HHS / United States K24MH097673 / MH / NIMH NIH HHS / United States P30MH062512 / MH / NIMH NIH HHS / United States R21DA036423 / DA / NIDA NIH HHS / United States P50DA026306 / DA / NIDA NIH HHS / United States R01MH092225 / MH / NIMH NIH HHS / United States U24MH100928 / MH / NIMH NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States R01MH94159 / MH / NIMH NIH HHS / United States |