Soluble mediators of inflammation in HIV and their implications for therapeutics and vaccine development

Abstract

From early in the HIV epidemic it was appreciated that many inflammatory markers such as neopterin and TNF-α were elevated in patients with AIDS. With the advent of modern technology able to measure a broad array of cytokines, we now know that from the earliest points of infection HIV induces a cytokine storm. This review will focus on how cytokines are disturbed in HIV infection and will explore potential therapeutic uses of cytokines. These factors can be used directly as therapy during HIV infection, either to suppress viral replication or prevent deleterious immune effects of infection, such as CD4+ T cell depletion. Cytokines also show great promise as adjuvants in the development of HIV vaccines, which would be critical for the eventual control of the epidemic.

Figure 1

The proportional fold-change relative to baseline in plasma levels of selected analytes and viral load in 35 plasma donors with acute HIV infection is shown. Time is plotted in days relative to T0, the day of first detectable plasma HIV. Figure reused with permission from the Journal of Virology, originally published in [28].

Figure 2

Macrophage-produced cytokines and nitric oxide (NO) induce endothelium-associated cell adhesion molecules enabling macrophages to move to the brain parenchyma. Cytokines and NO drive continued activation, MMP disrupts neuronal survival-signals, and T cells kill infected cells leading to damage and dysfunction.

Figure 3

pIFN-α treatment blocks viral replication with limited side effects and restores perforin production/secretion. IL-2 and IL-7 therapy have no direct effect on replication but result in increased CD4+ T cells, Tregs with IL-2 and naïve and central memory with IL-7.