NDLI: 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

Content Provider	PubMed Central
Author	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.
Editor	Wilkinson, Robert J.
Copyright Year	2013
Abstract	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<0.0001). IL-8, which is induced by IL-1β, was also highly expressed in the HIV-infected group in the absence of stimulation, 43.7% compared to 1.9% in HIV-uninfected subjects, p<0.0001. Strikingly, high basal expression of IL-1β by monocytes predicted high IL-6 levels in the plasma, and high monocyte IL-6 responses in HIV-infected subjects. Hyper-inflammatory IL-1β enriched monocytes may be a major source of IL-6 production and systemic inflammation in HIV-infected adults, and may contribute to the risk for all-cause mortality and cardiovascular disease in treated HIV infection.
Related Links	http://dx.doi.org/10.1371/journal.pone.0075500
Starting Page	75500
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	9
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-09-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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