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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

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783392/
https://www.ncbi.nlm.nih.gov/pubmed/24086545
http://dx.doi.org/10.1371/journal.pone.0075500
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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.
author_facet 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.
author_sort Jalbert, Emilie
collection PubMed
description 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.
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spelling pubmed-37833922013-10-01 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 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. PLoS One Research Article 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. Public Library of Science 2013-09-25 /pmc/articles/PMC3783392/ /pubmed/24086545 http://dx.doi.org/10.1371/journal.pone.0075500 Text en © 2013 Jalbert et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783392/
https://www.ncbi.nlm.nih.gov/pubmed/24086545
http://dx.doi.org/10.1371/journal.pone.0075500
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