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.

CD4+ T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV

“…T cells can mediate inflammatory and anti-inflammatory effects through plasma cytokines. Therefore, we also assessed whether CGC + T cells were related to inflammatory markers and anti-inflammatory cytokines important in cardiometabolic disease ( 35 ). The frequency of CGC + CD4 + T cells correlated with hsCRP (p=0.01), IL-4 (p=0.04), IL-10 (p=0.04) but not IL-6 (p=0.5) ( Figures 8E-H ).…”

“…We measured interleukin (IL)-4, IL-10, IL-6, and highly sensitive reactive protein (hs-CRP) in plasma using a multiplex assay (Meso Scale Diagnostics, Rockville, MD) as previously published ( 35 ).…”

Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy

“…Systemic TNF-α and IL-17A are thought to contribute to increased CVD risk by mediating endothelial damage [ 40 , 41 ]. We also recently demonstrated an association between IL-4 with carotid plaque burden in PWH, suggesting a direct role of type 2 type response in atherosclerosis plaque development [ 42 ]. Our observation that the cytokine response was significantly increased in women is concerning and could explain the higher risk of CVD observed among the HIV-positive women with HIV in the SSA compared to the men [ 43 , 44 ].…”

The Relationship Between Impaired Coronary Endothelial Function and Systemic Markers of Inflammation in People Living With HIV

“…31 Among PWH, studies reporting associations between FMD and traditional cardiovascular risk factors, inflammatory markers, and other subclinical CVD measures have shown variable results. 32–37…”