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

Sean Leng, Stewart Dandorf, Huifen Li, Joshua Carlson, Jessica Hui, Shruti Hemendra Mehta, Damani Arnold Piggott, Salequl Islam, Bhavish Manwani, Gregory D Kirk

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Pages (from-to)1257-1264
Number of pages8
JournalAIDS Research and Human Retroviruses
Issue number12
Publication statusPublished - Dec 1 2015


ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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