# The effect of age on xenobiotic-induced autoimmunity

> **NIH NIH UH3** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $99,850

## Abstract

Aging is associated with dysregulation of immune function manifested by increased susceptibility
to infections and an increase in chronic inflammation. Such chronic inflammation, especially the
presence of proinflammatory cytokines (IL-6, TNF-α), are predictors of failing immune status and
mortality in the elderly. Associated with these changes is an increase in autoantibody responses
and some autoimmune diseases. Environmental factors play a significant role in the development
of human autoimmunity, however age has not figured significantly in studies on environmentally-
induced autoimmunity other than the observation that occupational exposure is a significant
factor. Mercury exposure has been implicated in the expression of autoimmunity in humans and
experimental animal models. The human populations at risk are sizable and diverse. We have
extensive experience in the use of murine mercury-induced autoimmunity (mHgIA) as an
experimental model to study the initiation and development of systemic autoimmunity. The animal
age at exposure in these studies have ranged from 4-12 weeks with the length of exposure usually
being 4 weeks. Disease severity is dependent upon the presence of IFN-γ and IL-6, and localized
inflammatory response associated with increased proinflammatory cytokines including IL-1β, IFN-
γ and TNF-α. It remains unknown if induction of autoimmunity by mercury is exacerbated by the
age-related chronic inflammation and proinflammatory cytokine expression found in both humans
and mice. The importance of proinflammatory cytokines such as IL-6, TNF-α and IFN-γ in aging
and in mHgIA and idiopathic autoimmunity suggests that aging will lead to exacerbation of mHgIA
compared to younger animals. This application will test the hypothesis that "advanced age
impacts the experimental outcomes of mHgIA used to study environmentally-induced
autoimmunity in adult human populations." The proposed research will proceed in two phases as
outlined in the FOA (RFA-AG-16-020). The UH2 phase will focus on breeding cohorts of animals
up to the 75% survival level of B10.S, B10.S/Ifng-/- and B10.S/Il6-/- mice and includes a cohort to
be used for a preliminary test of the feasibility of using aged animals to induce mHgIA. The UH3
phase will compare the central hypothesis that “older ages of animals impact experimental
outcomes” by comparing and contrasting mHgIA in old versus young male and female B10.S
mice. We will also use B10.S/Ifng-/- and B10.S/Il6-/- mice to examine the contribution of IL-6 and
IFN-γ to age associated proinflammatory responses and whether they are requited for
development of age-related autoimmunity, and whether exposure to HgCl2 exacerbates
autoimmunity in aged animals deficient in either IL-6 or IFN-γ.

## Key facts

- **NIH application ID:** 10002226
- **Project number:** 5UH3ES027679-05
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Kenneth Michael Pollard
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $99,850
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002226

## Citation

> US National Institutes of Health, RePORTER application 10002226, The effect of age on xenobiotic-induced autoimmunity (5UH3ES027679-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10002226. Licensed CC0.

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