Interactions between prostaglandins, leukotrienes and HIV-1: Possible implications for the central nervous system

Abstract

In HIV-1-infected individuals, there is often discordance between viremia in peripheral blood and viral load found in the central nervous system (CNS). Although the viral burden is often lower in the CNS compartment than in the plasma, neuroinflammation is present in most infected individuals, albeit attenuated by the current combined antiretroviral therapy. The HIV-1-associated neurological complications are thought to result not only from direct viral replication, but also from the subsequent neuroinflammatory processes. The eicosanoids - prostanoids and leukotrienes - are known as potent inflammatory lipid mediators. They are often present in neuroinflammatory diseases, notably HIV-1 infection. Their exact modulatory role in HIV-1 infection is, however, still poorly understood, especially in the CNS compartment. Nonetheless, a handful of studies have provided evidence as to how these lipid mediators can modulate HIV-1 infection. This review summarizes findings indicating how eicosanoids may influence the progression of neuroAIDS.

Proinflammatory and Immunoregulatory Roles of Eicosanoids in T Cells

“…This conversion of membrane phospholipids into potent signaling mediators provides an efficient way for cells to respond to various stimuli that require a cellular response. As part of a complex network of regulators controlling a number of important physiological properties including smooth muscle tone, vascular permeability, and platelet aggregation, eicosanoids have also been implicated in a wide array of pathophysiological processes and diseases, including inflammation, autoimmunity, allergy, HIV, and cancer (Harizi et al, 2008; Greene et al, 2011; Bertin et al, 2012). While eicosanoids, in particular prostaglandins, were originally thought of primarily as proinflammatory mediators given their high expression in inflamed tissues and ability to induce inflammatory symptoms, this picture has over time become more nuanced.…”

Chronic Lithium Feeding Reduces Upregulated Brain Arachidonic Acid Metabolism in HIV-1 Transgenic Rat

“…Neurocognitive dysfunction in patients is considered to be initiated and driven by HIV-1 virus invasion and replication within the brain parenchyma, largely through productive infection of perivascular macrophages and endogenous microglia, and it is associated with neuroinflammation, reduced synaptic and dendritic density, and neuronal loss (Gray et al 1991; Masliah et al 1997; Yadav and Collman 2009; Kaul 2009; Bertin et al 2012). Despite the great success of highly active anti-retroviral therapy (HAART), drug resistance, toxicity, large HIV-1 genetic variability and inter-subtype circulating recombinant forms, as well as limited penetration of anti-retroviral drugs into the brain, remain concerns for many patients (Schouten et al 2011; Sigal et al 2011; Varatharajan and Thomas 2009).…”

Pathobiology of CNS Human Immunodeficiency Virus Infection

“…56 Arachidonic acid itself is excitotoxic to neurons, and additionally it is metabolized via the COX or lipoxygenase pathway. Its metabolism produces prostaglandins, prostacyclins, thromboxanes, and leukotrienes (eicosanoids).…”