Interleukin-17A is associated with flow-mediated dilation and interleukin-4 with carotid plaque in persons with HIV.

Abstract

OBJECTIVE:

Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on innate and adaptive immune cells, including innate lymphoid cells (ILCs) and CD4+ T-helper cells. At present, the relationship between CVD and plasma cytokines reflecting ILC/T-helper responses in PWH is not well defined. We investigated relationships between plasma cytokines and subclinical atherosclerosis.

DESIGN:

A cross-sectional study.

METHODS:

We recruited 70 PWH on a single antiretroviral regimen (efavirenz, teno- fovir, and emtricitabine) with at least 12 months of suppressed viremia and 30 HIVnegative controls. We quantified plasma cytokines and chemokines, including inter- feron-g, interleukin (IL)-4, IL-13, and IL-17A, markers of macrophage activation, and markers of endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward's hierarchical clustering. Brachial artery flow-mediated dilation (FMD) and carotid plaque burden were determined using ultrasound. Multivariable linear regression and negative binomial regression analyses were used to assess the relationships of plasma biomarkers and endpoints adjusted for CVD risk factors.

RESULTS:

We identified three distinct clusters in PWH, one containing Th1/Th2/ILC1/ ILC2 type cytokines, one with Th17/ILC3/macrophage-related cytokines, and a less specific third cluster. Lower FMD was associated with higher plasma IL-17A and macrophage inflammatory protein-1 a. In contrast, IL-4, a Th2/ILC2 type cytokine, was associated with carotid plaque. When HIV-negative controls were added to the models clustering was more diffuse, and these associations were attenuated or absent.

CONCLUSION:

Th17/ILC3 and Th2/ILC2-mediated immune mechanisms may have distinct roles in endothelial dysfunction and atherosclerotic plaque formation, respectively, in PWH.

• Authors: Celestine N Wanjalla, Tecla M Temu, Mona Mashayekhi, Christian M Warren, Bryan E Shepherd, Rama Gangula, Hubaida Fuseini, Samuel Bailin, Curtis L Gabriel, Pandu Gangula, Meena S Madhur, Spyros Kalams, Simon A Mallal, David G Harrison, Joshua A Beckman, John R Koethe
• Journal: AIDS (London, England) (AIDS) Vol. 36 Issue 7 Pg. 963-973 (06 01 2022) ISSN: 1473-5571 [Electronic] England
• PMID: 35165215 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Biomarkers
• Cytokines
• Interleukin-17
• Interleukin-4

Topics

• Atherosclerosis (complications)
• Biomarkers
• Cross-Sectional Studies
• Cytokines
• Dilatation
• HIV Infections (complications)
• Humans
• Immunity, Innate
• Interleukin-17
• Interleukin-4
• Plaque, Atherosclerotic
• Th17 Cells