# CMA: Immune/inflammatory priming in exacerbating responses to GWVI stressors: implications for GWVI treatments

> **NIH VA I01** · JAMES J PETERS VA  MEDICAL CENTER · 2024 · —

## Abstract

Project Summary/Abstract
This Collaborative Merit Review Award for Research (I01) proposed in response to RFA BX-18-007 from the
Veteran Health Administration is a joint effort by investigators from the JJ Peters VA Medical Center (Bronx,
NY) Project 1, Arnold School of Public Health and Wm Jennings Bryan Dorn VA Medical Center (Columbia,
SC) Project 2, Brain Science Center VA Medical Center (Minneapolis, MN) Project 3. We define a vision for
an integrated and multidisciplinary program of preclinical research projects all linked by the ultimate goal to
better characterize the mechanism of persistent and aberrant immunological activity in Gulf War Veteran
Illnesses (GWVI) by developing experimental model systems, with the ultimate goal of developing novel
therapeutic interventions. Gulf War Veterans’ Illnesses is a multifaceted disorder characterized by a range of
symptoms including cognitive impairment, fatigue, pain, mood disorders, among others. Recent evidence
suggests that the onset and progression of these symptoms may be the result of disequilibrium in these
subjects’ immune systems. During deployment GWV were exposed to a unique variety of toxic agents that
were specific to the Gulf War theatre, such as pyridostigmine bromine (PB), diisopropyl fluorophosphates
(DFP), permethrin, and depleted uranium which current evidence indicates lowered thresholds to
immunological responses and resulted in the persistent and heightened activity of certain arms of the immune
system; a phenomenon best described as “immunological priming”. In addition, they received more than 20
vaccines that could have overloaded the immune system. In support of these considerations, subjects with
GWVI often have shown pathological signatures in common with autoimmune disorders and generalized
inflammatory disorders, such as increased plasma concentrations of pro-inflammatory cytokines, unspecific
tissue degeneration, and organ failure. Based on this concept, the three proposed collaborative research
projects were designed to better understand how primed immune systems may contribute to GWVI- type
phenotypes by exploring how multiple GWI conditions recapitulated in animal models may synergize and
eventually provide new mechanistic evidence for translation studies. For example, Project 2 was designed to
understand how GW toxin induced gut inflammasome activation causes gut dysbiosis and may lead to
persistent or heightened immune-inflammatory responses and GWVI symptoms. As the goal of Project 3 is
designed the hypothesis that lack of specific immunity leads to vaccine-induced inflammatory reaction in the
brain, Project 2 will collaborate with project 3 to test the contribution of inflammasome priming and genetic
diversity to gut dysbiosis and persistent immunological responses. Similarly, Project 1, which is designed to
test how immunological priming may heighten inflammatory responses to psychological stressors, will
collaborate with project 2 and project 3 by exploring ...

## Key facts

- **NIH application ID:** 11087453
- **Project number:** 5I01BX004583-06
- **Recipient organization:** JAMES J PETERS VA  MEDICAL CENTER
- **Principal Investigator:** Giulio Maria Pasinetti
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11087453

## Citation

> US National Institutes of Health, RePORTER application 11087453, CMA: Immune/inflammatory priming in exacerbating responses to GWVI stressors: implications for GWVI treatments (5I01BX004583-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11087453. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*