IL-1Β enriched monocytes mount massive IL-6 responses to common inflammatory triggers among chronically HIV-1 infected adults on stable anti-retroviral therapy at risk for cardiovascular disease

• Published in: PloS one 2013-09, Vol.8 (9), p.e75500-e75500
• Main Authors: Jalbert, Emilie, Crawford, Timothy Q, D'Antoni, Michelle L, Keating, Sheila M, Norris, Philip J, Nakamoto, Beau K, Seto, Todd, Parikh, Nisha I, Shikuma, Cecilia M, Ndhlovu, Lishomwa C, Barbour, Jason D
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adults; AIDS; Anti-Retroviral Agents - therapeutic use; Antiretroviral agents; Antiretroviral therapy; Arteriosclerosis; Atherosclerosis; Biomarkers; Blood; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - etiology; Cardiovascular Diseases - immunology; Cardiovascular Diseases - metabolism; Chronic infection; Cryopreservation; Cytometry; Female; Flow cytometry; Health risks; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - metabolism; HIV-1 - drug effects; HIV-1 - immunology; Human immunodeficiency virus; Humans; Infections; Inflammation; Inflammation - immunology; Inflammation - metabolism; Interleukin 6; Interleukin 8; Interleukin-1beta - immunology; Interleukin-1beta - metabolism; Interleukin-6 - immunology; Interleukin-6 - metabolism; Interleukin-8 - immunology; Interleukin-8 - metabolism; Intracellular; Lipopolysaccharides; Male; Middle Aged; Monocytes; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Mortality; Peripheral blood; Plasma levels; Risk; Stimulation; Therapy; Tumor necrosis factor; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0075500

Chronic infection by HIV increases the risk of cardiovascular disease (CVD) despite effective antiretroviral therapy (ART). The mechanisms linking HIV to CVD have yet to be fully elucidated. High plasma levels of the pro-inflammatory cytokine IL-6, which may be triggered by IL-1β, is a biomarker of CVD risk in HIV-negative adults, and of all-cause mortality in HIV disease. Monocytes play a pivotal role in atherosclerosis, and may be major mediators of HIV-associated inflammation. We therefore hypothesized that monocytes from HIV-infected adults would display high inflammatory responses. Employing a 10-color flow cytometry intracellular cytokine staining assay, we directly assessed cytokine and chemokine responses of monocytes from the cryopreserved peripheral blood of 33 chronically HIV-1 infected subjects. Participants were 45 years or older, on virologically suppressive ART and at risk for CVD. This group was compared to 14 HIV-negative subjects matched for age and gender, with similar CVD risk. We simultaneously detected intracellular expression of IL-1β, IL-6, IL-8 and TNF in blood monocytes in the basal state and after stimulation by triggers commonly found in the blood of treated, chronically HIV-infected subjects: lipopolysaccharide (LPS) and oxidized low-density lipoprotein (oxLDL). In the absence of stimulation, monocytes from treated HIV-infected subjects displayed a high frequency of cells producing IL-1β (median 19.5%), compared to low levels in HIV-uninfected persons (0.9% p