# SSRIs Inhibit IgE-mediated Mast Cell Function

> **NIH NIH R21** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $182,271

## Abstract

PROJECT SUMMARY
Mast cells function as innate sentinels, whose activation protects the host from infection but can also
cause pathological inflammation. Therefore, new ways of intervening in mast cell function can benefit
unmet clinical needs. A significant knowledge gap in immunology is the connection between inflammation
and depression. These data are bi-directional: depression is common among patients with chronic
inflammation; anti-inflammatory drugs can improve clinical depression; and anti-depressants have anti-
inflammatory effects (1-8). These findings include an association between allergic disease and
depression (9, 10). These links prompted us to examine effects of the commonly prescribed anti-
depressants, selective serotonin reuptake inhibitors (SSRIs), on IgE-mediated mast cell function. We find
that SSRIs suppress IgE- mediated mast cell degranulation and cytokine secretion in vitro and systemic
anaphylactic shock in vivo. SSRI effects may be due to inhibiting purinergic receptors of the P2X family -
ATP-gated ion channels expressed on neurons and many immune cells, including mast cells (11-17).
ATP is rapidly released by IgE-activated mast cells (18), is elevated in inflamed tissues, and exacerbates
inflammation by activating P2X receptors (19). Although the importance for P2X receptors in immune
function is accepted, little is known about purinergic signaling in mast cells, how this is related to allergic
disease, and any connection to SSRI therapy. We recently found that the suppressive effects of the SSRI
fluoxetine are absent on mast cells lacking P2X3. Therefore, this project will test the hypothesis that
SSRIs suppress IgE-mediated mast cell activation by inhibiting P2X3 function, preventing ATP-mediated
exacerbation of allergic inflammation.

## Key facts

- **NIH application ID:** 9825511
- **Project number:** 5R21AI138494-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** John J Ryan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $182,271
- **Award type:** 5
- **Project period:** 2018-11-19 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825511

## Citation

> US National Institutes of Health, RePORTER application 9825511, SSRIs Inhibit IgE-mediated Mast Cell Function (5R21AI138494-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9825511. Licensed CC0.

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