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Open Access Research article

Cytokine secretion from brain macrophages infected with human immunodeficiency virus in vitro and treated with raltegravir

Erick T Tatro1*, Benchawanna Soontornniyomkij1, Scott L Letendre2 and Cristian L Achim1

Author Affiliations

1 Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0603, USA

2 Department of Medicine, University of California San Diego, 200 West Arbor Drive, San Diego, CA 92103-8208, USA

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BMC Infectious Diseases 2014, 14:386  doi:10.1186/1471-2334-14-386

Published: 11 July 2014

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.

Keywords:
Microglia; Human immunodeficiency virus; Integrase inhibitor; Raltegravir; IL-10; IL-8; TNF-α