Cytokine secretion from brain macrophages infected with human immunodeficiency virus in vitro and treated with raltegravir
Year: 2014
Type: article
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.
Source: BMC Infectious Diseases
Institution: University of California San Diego
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,090
Awards: Translational Methamphetamine AIDS Research Center (TMARC), Clinical Trial of CNS Penetrating ART to Prevent NeuroAIDS in China, California NeuroAIDS Tissue Network, G3512707296, G4342692216, G5641659859, Long Term Effects of Chronic HIV Infection on the Developing Brain, G7832932932, Midcareer Investigator Award in Patient-Oriented NeuroAIDS Research, San Diego Center for AIDS Research (SD CFAR), HIV Neurobehavioral Research Center
OpenAlex ID: W2010025849