title: Associations of Circulating Soluble Tumor Necrosis Factor-α Receptors 1 and 2 with Interleukin-6 Levels in an Aging Cohort of Injection Drug Users with or at High Risk for HIV Infection.
abstract: Chronic inflammation marked by elevated interleukin (IL)-6, soluble tumor necrosis factor (TNF)-α receptor (sTNFR)-1, and sTNFR-2 levels may play a detrimental role in aging and HIV infection. This study aimed to evaluate the relationships of circulating IL-6 with sTNFR-1 and sTNFR-2 levels in an aging cohort of injection drug users (IDUs) with or at high risk for HIV infection. The AIDS Linked to the Intravenous Experience (ALIVE) study is a community-recruited, prospective observational study of former and current IDUs in Baltimore, Maryland. Serum IL-6, sTNFR-1, and sTNFR-2 levels were measured using standard ELISA. Multivariate linear regression analysis was employed, adjusting for age, sex, HIV status, injection drug use, comorbidities, as well as HIV viral load, CD4 T cell counts, and antiretroviral therapy where appropriate. The analysis included 1,178 participants (316 HIV positive and 862 HIV negative). In the adjusted model, sTNFR-1 and sTNFR-2 were individually associated with IL-6 (regression coefficient: 0.877 and 0.556, respectively, for all participants; 0.607 and 0.407 for HIV positives; and 0.999 and 0.628 for HIV negatives, all p < 0.0001). In the model combining sTNFR-1 and sTNFR-2, the associations for sTNFR-1 remained significant (0.693 for all participants, p < 0.0001; 0.417 for HIV positives, p < 0.05; and 0.840 for HIV negatives), while those for sTNFR-2 were no longer significant. sTNFR-1 and sTNFR-2 were positively associated with IL-6 in ALIVE participants. These findings provide initial insight into the in vivo relationship between TNF-α activation and IL-6 and a basis for further investigations into potential mechanisms underlying chronic inflammation in aging and HIV infection.
authors.affiliation: 1 Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University Schools of Medicine , Baltimore, Maryland.
authors.forename: Sean X
authors.initials: SX
authors.lastname: Leng
authors.affiliation: 1 Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University Schools of Medicine , Baltimore, Maryland.
authors.forename: Stewart
authors.initials: S
authors.lastname: Dandorf
authors.affiliation: 1 Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University Schools of Medicine , Baltimore, Maryland.
authors.forename: Huifen
authors.initials: H
authors.lastname: Li
authors.affiliation: 1 Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University Schools of Medicine , Baltimore, Maryland.
authors.forename: Joshua
authors.initials: J
authors.lastname: Carlson
authors.affiliation: 1 Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University Schools of Medicine , Baltimore, Maryland.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hui
authors.affiliation: 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Shruti H
authors.initials: SH
authors.lastname: Mehta
authors.affiliation: 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Damani
authors.initials: D
authors.lastname: Piggott
authors.affiliation: 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Salequl
authors.initials: S
authors.lastname: Islam
authors.affiliation: 1 Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University Schools of Medicine , Baltimore, Maryland.
authors.forename: Bhavish
authors.initials: B
authors.lastname: Manwani
authors.affiliation: 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D015142:Baltimore; D005260:Female; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D015819:Substance Abuse, Intravenous / Q000473:pathology*; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II