TY - JOUR
T1 - Differential relationships among circulating inflammatory and immune activation biomediators and impact of aging and human immunodeficiency virus infection in a cohort of injection drug users
AU - Kirk, Gregory D.
AU - Dandorf, Stewart
AU - Li, Huifen
AU - Chen, Yiyin
AU - Mehta, Shruti H.
AU - Piggott, Damani A.
AU - Margolick, Joseph B.
AU - Leng, Sean X.
N1 - Funding Information:
The authors would like to thank the ALIVE study participants and staff for their contributions to this research., This work is supported in part by NIH grant R01-DA-004334, U01-DA-036297 and RC1-AI-086053 (PI: GK), R01-DA-12568 (PI: SM), R21-AG-043874 (PI: SL), R01-AI-108907 (PI: SL), and funding from the Irma and Paul Milstein Program for Senior Health of the Milstein Medical Asian and American Partnership (MMAAP) Foundation (www.mmaapf.org) (to SL). SL has overseen the study described in this manuscript.
Publisher Copyright:
© 2017 Kirk, Dandorf, Li, Chen, Mehta, Piggott, Margolick and Leng.
PY - 2017/10/19
Y1 - 2017/10/19
N2 - As individuals with human immunodeficiency virus (HIV) infection live longer, aging and age-related chronic conditions have become major health concerns for this vulnerable population. Substantial evidence suggests that chronic inflammation and immune activation contribute significantly to chronic conditions in people aging with or without HIV infection. As a result, increasing numbers of inflammation and immune activation biomediators have been measured. While very few studies describe their in vivo relationships, such studies can serve as an important and necessary initial step toward delineating the complex network of chronic inflammation and immune activation. In this study, we evaluated in vivo relationships between serum levels of neopterin, a biomediator of immune activation, and four commonly described inflammatory biomediators: soluble tumor necrosis factor (TNF)-α receptor (sTNFR)-1, sTNFR-2, interleukin (IL)-6, and C-reactive protein (CRP), as well as the impact of HIV infection and aging in the AIDS Linked to the Intravenous Experience (ALIVE) study, a community-recruited observational study of former and current injection drug users (IDUs) with or at high risk for HIV infection in Baltimore, MD, USA. The study included 1,178 participants in total with 316 HIV-infected (HV+) and 862 HIV-uninfected (HIV-) IDUs. Multivariate regression analyses were employed, adjusting for age, sex, body mass index, smoking, hepatitis C virus co-infection, injection drug use, comorbidities, and HIV status (for all participants), and HIV viral load, CD4+ T-cell counts, and antiretroviral therapy (for HIV+ participants). The results showed significant impact of aging on all five biomediators and that of HIV infection on all but sTNFR-1. In the adjusted model, neopterin had positive associations with sTNFR-1 and sTNFR-2 (partial correlation coefficients: 0.269 and 0.422, respectively, for all participants; 0.292 and 0.354 for HIV+; and 0.262 and 0.435 for HIV-, all p < 0.0001). No significant associations between neopterin and IL-6 or CRP were identified. Such differential relationships between circulating neopterin and sTNFR-1, sTNFR-2, IL-6, and CRP may help inform their selection in future studies. These findings may also facilitate elucidation of underlying inflammatory and immune activation pathways that contribute to age-related chronic conditions, potentially leading to identification of key biomediators, particularly those upstream of CRP, as novel targets for intervention.
AB - As individuals with human immunodeficiency virus (HIV) infection live longer, aging and age-related chronic conditions have become major health concerns for this vulnerable population. Substantial evidence suggests that chronic inflammation and immune activation contribute significantly to chronic conditions in people aging with or without HIV infection. As a result, increasing numbers of inflammation and immune activation biomediators have been measured. While very few studies describe their in vivo relationships, such studies can serve as an important and necessary initial step toward delineating the complex network of chronic inflammation and immune activation. In this study, we evaluated in vivo relationships between serum levels of neopterin, a biomediator of immune activation, and four commonly described inflammatory biomediators: soluble tumor necrosis factor (TNF)-α receptor (sTNFR)-1, sTNFR-2, interleukin (IL)-6, and C-reactive protein (CRP), as well as the impact of HIV infection and aging in the AIDS Linked to the Intravenous Experience (ALIVE) study, a community-recruited observational study of former and current injection drug users (IDUs) with or at high risk for HIV infection in Baltimore, MD, USA. The study included 1,178 participants in total with 316 HIV-infected (HV+) and 862 HIV-uninfected (HIV-) IDUs. Multivariate regression analyses were employed, adjusting for age, sex, body mass index, smoking, hepatitis C virus co-infection, injection drug use, comorbidities, and HIV status (for all participants), and HIV viral load, CD4+ T-cell counts, and antiretroviral therapy (for HIV+ participants). The results showed significant impact of aging on all five biomediators and that of HIV infection on all but sTNFR-1. In the adjusted model, neopterin had positive associations with sTNFR-1 and sTNFR-2 (partial correlation coefficients: 0.269 and 0.422, respectively, for all participants; 0.292 and 0.354 for HIV+; and 0.262 and 0.435 for HIV-, all p < 0.0001). No significant associations between neopterin and IL-6 or CRP were identified. Such differential relationships between circulating neopterin and sTNFR-1, sTNFR-2, IL-6, and CRP may help inform their selection in future studies. These findings may also facilitate elucidation of underlying inflammatory and immune activation pathways that contribute to age-related chronic conditions, potentially leading to identification of key biomediators, particularly those upstream of CRP, as novel targets for intervention.
KW - CRP
KW - Human immunodeficiency virus infection and aging
KW - IL-6
KW - Neopterin
KW - STNFR-1
KW - STNFR-2
UR - http://www.scopus.com/inward/record.url?scp=85031725719&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031725719&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.01343
DO - 10.3389/fimmu.2017.01343
M3 - Article
C2 - 29097998
AN - SCOPUS:85031725719
SN - 1664-3224
VL - 8
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - OCT
M1 - 1343
ER -