Sutherlandia frutescens may exacerbate HIV-associated neuroinflammation.

Luan Dane Africa,Carine Smith

doi:10.1186/s12952-015-0031-y

Luan Dane Africa, Carine Smith

Open Access

https://doi.org/10.1186/s12952-015-0031-y

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Abstract

BackgroundNeuroinflammation is central to the aetiology of HIV-associated neurocognitive disorders (HAND) that are prevalent in late stage AIDS. Anti-retroviral (ARV) treatments are rolled out relatively late in the context of neuroinflammatory changes, so that their usefulness in directly preventing HAND is probably limited. It is common practice for HIV+ individuals in developing countries to make use of traditional medicines. One such medicine is Sutherlandia frutescens - commonly consumed as a water infusion. Here its efficacy as an anti-inflammatory modality in this context was investigated in an in vitro co-culture model of the blood–brain barrier (BBB).MethodsSingle cultures of human astrocytes (HA), HUVECs and primary human monocytes, as well as co-cultures (BBB), were stimulated with HIV-1 subtype B & C Tat protein and/or HL2/3 cell secretory proteins after pre-treatment with S.frutescens extract. Effects of this pre-treatment on pro-inflammatory cytokine secretion and monocyte migration across the BBB were assessed.ResultsIn accordance with others, B Tat was more pro-inflammatory than C Tat, validating our model. S.frutescens decreased IL-1β secretion significantly (P < 0.0001), but exacerbated both monocyte chemoattractant protein-1 (P < 0001) – a major role player in HIV-associated neuroinflammation – and CD14+ monocyte infiltration across the BBB (P < 0.01).ConclusionsCurrent data illustrates that the combined use of HL2/3 cells and the simulated BBB presents an accurate, physiologically relevant in vitro model with which to study neuroinflammation in the context of HIV/AIDS. In addition, our results caution against the use of S.frutescens as anti-inflammatory modality at any stage post-HIV infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12952-015-0031-y) contains supplementary material, which is available to authorized users.

Highlights

Neuroinflammation in the context of HIV/Acquired immune deficiency syndrome (AIDS) is known to have onset soon after infection with the virus and is associated with the HIV-associated neurocognitive disorders (HAND) that are prevalent in late stage AIDS [1]
Due to the fact that S. frutescens had not, up until this point, been tested on the cell types used in this study, it was important to first establish the optimal dose for use in vitro, prior to assessment of S. frutescens as an effective anti-inflammatory modality
Monocyte chemoattractant protein-1 (MCP-1) responses were evaluated in human astrocytes, human umbilical vein endothelial cell (HUVEC), primary human monocyte and blood–brain barrier (BBB) co-cultures following stimulation with Human Immunodeficiency virus type −1 (HIV-1) subtype B & C Tat protein, and HL2/3 conditioned media in the case of astrocytes, HUVECs and monocytes, and co-culturing BBB cultures with HL2/3 cells

Summary

Introduction

Neuroinflammation in the context of HIV/AIDS is known to have onset soon after infection with the virus and is associated with the HIV-associated neurocognitive disorders (HAND) that are prevalent in late stage AIDS [1]. Conventional anti-retroviral treatments are rolled out relatively late in the context of neuroinflammatory changes, so that their usefulness in directly preventing HAND is probably limited. It is clear that early prevention strategies to limit the Traditional medicine is commonly used by those living with HIV infection, in developing countries One such complementary medicine that is widely used, is Sutherlandia frutescens Anti-retroviral (ARV) treatments are rolled out relatively late in the context of neuroinflammatory changes, so that their usefulness in directly preventing HAND is probably limited. It is common practice for HIV+ individuals in developing countries to make use of traditional medicines. Its efficacy as an anti-inflammatory modality in this context was investigated in an in vitro co-culture model of the blood–brain barrier (BBB)

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