Inflammation-modulating cytokine profile and lipid interaction in HIV-related risk factors for cardiovascular diseases

Abstract

HIV infection and antiretroviral therapy (ART) are associated with changes in plasma levels of lipoproteins, thus posing the risk of cardiovascular complications in infected individuals. The alteration in plasma lipoprotein levels results from dysregulation of inflammation-modulating cytokines that control lipid metabolism. Little is understood regarding the relationship between the cytokines and serum lipid levels, which have been reported to be altered in adults receiving ART. The objective of this study was to describe the profiles of inflammation-modulating cytokines and their relationship to lipids as cardiovascular disease (CVD) risk factors in HIV infection. This observational cross-sectional study measured plasma levels of interleukin (IL)-10, tumor necrosis factor-alpha (TNF)-α, IL-4, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-c) in HIV-infected and uninfected adults. A total of 219 HIV-infected participants were enrolled from an HIV treatment center; of them, 187 were receiving ART and 32 were ART naïve, while 65 were HIV-uninfected blood donors. HIV-infected individuals had higher levels of IL-10 (HIV-infected ART-naïve [P=0.0024] and ART-receiving [P=0.033]) than their uninfected counterparts. ART-naïve subjects had significantly higher plasma levels of IL-10 than ART-receiving subjects (P=0.0014). No significant difference was observed in plasma levels of IL-4 and TNF-α across the three groups. Regarding plasma lipoproteins, HDL-c levels were reduced in HIV ART-naïve (P=0.002) and ART-receiving (P=0.015) subjects compared to HIV-uninfected subjects. Similarly, TC levels were lower in the HIV-infected than in the HIV-uninfected group regardless of whether the patients were undergoing ART or not (P<0.001). IL-10 levels correlated with TC levels in the HIV-uninfected group but not in the HIV-infected groups. Levels of HDL-c were reduced, while IL-10 plasma concentrations were elevated in HIV-infected individuals. A correlation observed in HIV-uninfected individuals between anti-inflammatory cytokine IL-10 and TC was lost in HIV-infected individuals. Clinical significance of these differences needs to be ascertained with respect to HIV-related CVD risk.

Inflammatory Markers and Plasma Lipids in HIV Patients: A Correlation Analysis Study

“…The level of IL-10, an anti-inflammatory cytokine, was significantly elevated (p=0.020) in ART-experienced patients compared to ART-naive patients in this study, which is in contrast to a report from another Zimbabwean study [ 44 ]. The difference may be due to differences in time points at which these studies were carried out: Gori et al [ 44 ] at baseline and our current study at follow-up, on sub-populations of the same cohort [ 8 , 22 ]. Our study supports the hypothesis that patients on antiretroviral treatment have reduced levels of inflammatory markers, a possible mechanism for control of inflammation in ART positive patients [ 28 , 36 ].…”

“…The plasma level of high sensitivity CRP was elevated in all the HIV infected patients in agreement with another South African study [ 31 ]. A substantial body of evidence associates this inflammatory marker with increased coronary heart disease risk [ 24 , 44 , 45 ]. There were, however, no association between hsCRP, TNF-α or IL-10 levels with most lipids (TC, LDL-C, HDL-C, TC/HDL-C ratio) in our current study.…”

Cytokine’s Imbalance, the Hallmark of Immune Dysfunction in HIV/AIDS Patients in Rwanda

“…The sample size was estimated using the two groups comparison formula by Lwanga et al, 1990and 1991(Lemeshow & Lwanga, 1990Lwanga & Lemeshow, 1991) as follows: Whereby: SD is the Standard deviation of the mean of cytokines the two populations. The IL-4 showed to be highly varied in HIV and its SD was used in the sample size estimation formula 38 pg/ ml and 41 pg/ ml for ART naïve and patients on HAART respectively (Gori et al, 2016) d = Expected precision. Mean difference of variables between the groups that is associated with clinical difference.…”

HIV and Cardiovascular Disease: Role of Immunometabolic Perturbations

“…Higher ROS levels can also activate transforming growth factor beta (TGF-␤), which can induce regulatory T (Treg) cells during HIV infection, contributing to the imbalance with T helper (TH) cells (1) (discussed later). The HIV-mediated pro-inflammatory response may promote pro-oxidative alterations of specific lipid species, such as oxidized low-density lipoprotein (OX-LDL) (22,33), that contribute to increased monocyte and T-lymphocyte infiltration into vascular walls (14,65). There is strong evidence that innate immune activation plays an important role in HIV pathogenesis and that its components may contribute to the onset of atherosclerosis.…”

“…The early inflammation and immune activation associated with HIV infection may enhance lipid peroxidation, which is associated with decreased anti-oxidant capacity and a lower CD4 count in untreated asymptomatic HIV-infected individuals (74). Thus a persistent inflammatory environment together with relatively high levels of inflammatory cytokines may promote pro-inflammatory alterations of the lipid profile in HIV-positive persons (22,33) (FIGURE 3). This in turn can lead to increased OX-LDL formation that further contributes to monocyte activation and increased risk for coronary artery disease onset (82).…”