# Role of IL-6 and IL-1b in immune dysfunction during aging, HIV, and HCV infection

> **NIH VA IK2** · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · 2021 · —

## Abstract

Chronic systemic inflammation is associated with immune dysfunction and morbidities in the elderly, treated
HIV infection, and HCV infection. We propose that circulating inflammatory proteins drive immune exhaustion
and senescence and contribute to the immune dysfunction seen in these patient groups. Nearly 4 million
Americans are infected with Hepatitis C Virus (HCV) and the mean age of US veterans infected with HCV is
nearing 65 years. Although the new IFN-free direct-acting antiviral therapy is highly effective at clearing virus
from patients, the patients are left with the consequences of decades of infection and liver damage, and it is
still unclear how long soluble mediators of inflammation persist, and how long immune dysfunction and
associated morbidity lasts. Similarly, even HIV-infected patients that have successfully controlled viral
replication with ART for decades have increased mortality and morbidity and persistent inflammation. The VA
is the largest single provider of HIV care in the US. Understanding what causes the continued morbidity in
these veteran patient populations is critical. The elderly, HCV and HIV-infected patients all have chronic
immune inflammation and these three patient groups share many of the same comorbidities including
cardiovascular disease, cancer, and liver disease. The project design of this CDA-2 application is based on the
understanding that patients with chronic viral infections and elderly patients show chronic elevated plasma
levels of IL-6, and our more recent data demonstrating elevated levels of IL-1β in lymph nodes of HIV-infected
patients. The central goals of this study are to determine the underlying mechanisms of IL-6 and IL-1β that
contribute to the development of immune exhaustion and senescence and to examine the potential therapeutic
role of temporarily blocking IL-6 and IL-1β during chronic infection to improve immune function and recovery of
exhausted or senescent T cells. The hypothesis that chronic elevated levels of IL-6 and IL-1β during aging,
HCV infection and HIV infection contribute to immune senescence and exhaustion and resulting immune
dysfunction will be tested in 3 specific Aims. Aim 1 will determine the phenotype and function of T cells that
have been exposed to IL-1β or IL-6 in vitro by sorting the cells positive for exhaustion or senescent markers
(PD-1, CD57, Tim-3, KLRG1, Lag3) and examining their functional abilities to determine if inflammatory
cytokines alone can drive senescence, independent of antigen exposure. Aim 2A will examine the expression
levels of exhaustion and senescent markers and the intracellular production of cytokines associated with the
senescence-associated secretory phenotype (SASP) in lymphocytess from HCV-infected, treated HIV-infected,
and elderly patients by flow cytometry. Aim 2B will examine the recovery and normalization of immune
function, longitudinally, in HIV-infected patients after initiation of ART and in HCV-infected patients after
i...

## Key facts

- **NIH application ID:** 9858239
- **Project number:** 5IK2CX001471-04
- **Recipient organization:** LOUIS STOKES CLEVELAND VA MEDICAL CENTER
- **Principal Investigator:** Carey Lynn Shive
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858239

## Citation

> US National Institutes of Health, RePORTER application 9858239, Role of IL-6 and IL-1b in immune dysfunction during aging, HIV, and HCV infection (5IK2CX001471-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9858239. Licensed CC0.

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