Inflammation, HIV, and Immune Quiescence: Leveraging on Immunomodulatory Products to Reduce HIV Susceptibility

Abstract

The relationship between inflammation and HIV has been a focus of research over the last decade. In HIV-infected individuals, increased HIV-associated immune activation significantly correlated to disease progression. While genital inflammation (GI) has been shown to significantly increase the risk of HIV acquisition and transmission, immune correlates for reduced risk remain limited. In certain HIV-exposed seronegative individuals, an immune quiescent phenotype characterized reduced risk. Immune quiescence is defined by specific, targeted, highly regulated immune responses that hinder overt inflammation or immune activation. Targeted management of inflammation, therefore, is a plausible strategy to mitigate HIV risk and slow disease progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as hydroxychloroquine and aspirin have shown encouraging preliminary results in low-risk women by reducing systemic and genital immune activation. A topical NSAID, containing ibuprofen, is effective in treating vulvovaginal inflammation. Additionally, the glucocorticoids (GCs), prednisolone, and dexamethasone are used to treat HIV-associated immune activation. Collectively, these data inform on immune-modulating drugs to reduce HIV risk. However, the prolonged use of these pharmaceutical drugs is associated with adverse effects, both systemically and to a lesser extent topically. Natural products with their reduced side effects coupled with anti-inflammatory properties render them viable options. Lactic acid (LA) has immunomodulatory properties. LA regulates the genital microbiome by facilitating the growth of Lactobacillus species, while simultaneously limiting bacterial species that cause microbial dysbiosis and GI. Glycerol monolaurate, besides being anti-inflammatory, also inhibited SIV infections in rhesus macaques. The proposed pharmaceutical and natural products could be used in combination with either antiretrovirals for treatment or preexposure prophylaxis for HIV prevention. This review provides a summary on the associations between inflammation, HIV risk, and disease progression. Furthermore, we use the knowledge from immune quiescence to exploit the use of pharmaceutical and natural products as strategic interventions to manage inflammation, toward mitigating HIV infections.

Glycerol Monolaurate Ameliorated Intestinal Barrier and Immunity in Broilers by Regulating Intestinal Inflammation, Antioxidant Balance, and Intestinal Microbiota

“…In this study, dietary GML effectively benefited the jejunal MUC 2 content and up-regulated ZO-1 and occludin expression, demonstrating the beneficial effect of GML on intestinal barrier of broilers. The TNF-α and IFN-γ are related to the reduction in epithelial barrier function and increases the permeability of the mucosal barrier ( 35 ). The reduction in serum TNF-α level and decrease in jejunal IFN-γ expression in this study supported the idea that GML mediates intestinal barrier function through a mechanism associated with the attenuation of intestinal inflammation.…”

Glycerol monolaurate ameliorated intestinal barrier and immunity in broilers by regulating intestinal inflammation, antioxidant balance, and intestinal microbiota

“…In this study, dietary GML effectively benefited the jejunal muc 2 content and up-regulated ZO-1 and occludin expression, demonstrating the beneficial effect of GML on intestinal barrier of broilers. The TNF-α and IFN-γ are related to the reduction in epithelial barrier function and increases the permeability of the mucosal barrier (31). The reduction in serum TNF-α level and decrease in jejunal IFN-γ expression in this study supported the idea that GML mediates intestinal barrier function through a mechanism associated with the attenuation of intestinal inflammation.…”

“…In this study, dietary GML effectively benefited the jejunal muc 2 content and up-regulated ZO-1 and occludin expression, demonstrating the beneficial effect of GML on intestinal barrier of broilers. The TNF-α and IFN-γ are related to the reduction in epithelial barrier function and increases the permeability of the mucosal barrier (31).…”

Extinguish the Fire: Anti-inflammatory Strategies for Over Immune Activation in Chronic HIV-1 Infection

“…However, the same group later carried out a randomized placebo-controlled trial, and found that aspirin treatment for 12 weeks resulted in no major impact on soluble CD14, IL-6, soluble CD163, d -dimer, T-cell, or monocyte activation, suggesting that inhibition of COX-1-mediated platelet activation may not significantly improve HIV-1-related immune activation [21] . Interestingly, daily low-dose aspirin was developed as an approach to decrease HIV-1 target cells at the female genital tract through systemic and local inflammation reduction, and preliminary results showed this may reduce HIV-1 susceptibility and become a novel HIV-prevention approach in low-risk women [22,23] …”