Reduced sTWEAK and Increased sCD163 Levels in HIV-Infected Patients: Modulation by Antiretroviral Treatment, HIV Replication and HCV Co-Infection

Abstract

BackgroundPatients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV.ObjectiveThe aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects.ResultsPatients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations.ConclusionHIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART.

Biomarkers of inflammation in HIV-infected Peruvian men and women before and during suppressive antiretroviral therapy

“…Specifically, the 24-month ART concentrations of hsCRP, interleukin-6, and sCD163 were increased in our Peruvian cohort relative to concentrations presented in other studies from the United States and Spain [27,30,36–39]. This may be because of the Peruvians having relatively more advanced HIV disease at the time of ART initiation, which may have led to a sustained compromise of their intestinal mucosa facilitating microbial translocation [19], differences in abdominal obesity [25], immune reconstitution inflammatory syndrome, or other factors.…”

Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm

“…High levels of sCD163 can be detected in plasma in a wide range of inflammatory diseases, including carotid- [62], peripheral- [16] and coronary-artery disease [63], as well as type 2 diabetes [48] and human immunodeficiency virus [64]. In our study, circulating sCD163 levels were similar between patients with AAA and control individuals, and no association was found between sCD163 and maximal aortic diameter, a surrogate marker of AAA growth.…”

The role of tumor necrosis factor-like weak inducer of apoptosis in atherosclerosis via its two different receptors

“…CD163 is a marker for anti-inflammatory activity in macrophages (57) and is potentially a newly identified receptor for TWEAK, as reported previously (18,21). Increasing in vivo and in vitro evidence suggests that the interaction between TWEAK and CD163 may affect the development of atherosclerosis and related diseases (19,20,(57)(58)(59)(60).…”