# Dysregulated Immune State in PTSD Contributes to Microglial Inflammation

> **NIH VA I01** · RALPH H JOHNSON VA MEDICAL CENTER · 2024 · —

## Abstract

Over 2.5 million U.S. service members have been deployed to Afghanistan or Iraq war zones since 2002 and,
according to reports from the Department of Veterans Affairs, one in every six returns from this OEF/OIF arena
with PTSD. Since only half of the Veterans with PTSD response to treatment, alternate treatment approaches
need to be explored. PTSD consists not only clusters of clinical symptoms, but also immune imbalances
toward an inflammatory state. Studies of humans and with animal models have shown that peripheral
inflammation can stimulate neuroinflammation and, in turn, alter behavior. Added studies have suggested
immune contributions to PTSD following trauma. However, immune analyses with PTSD subjects have been
haphazard and studies have not considered the possibility of restoring peripheral immune balance to lessen
neuroinflammation as a novel immunotherapeutic approach for PTSD.
The hypothesis of the present study is that the dysregulated immune state in PTSD parallels disease status,
and can contribute to inflammatory brain cell reactivity. Also hypothesized is that leukocytes from subjects with
PTSD can be redirected from a hyper-inflammatory state toward a balanced regulated state, thus quenching
their ability to stimulate brain cell inflammatory activity.
Rationale: While the present study does not propose inflammation to be the primary cause of PTSD, there is
support for a causative linkage between inflammation and PTSD following trauma exposure. Several studies
with human subjects showed that stimulation of peripheral inflammation results in activation of brain microglia,
hypervigilence, irritability and anxiety. If inflammation-skewed leukocytes of PTSD subjects still retain
plasticity, then then there is the opportunity for immune redirection to a functionally balanced state that does
not facilitate brain cell inflammatory activity. The following specific aims will test the hypothesis of this study:
Aim #1: Define the immune imbalances in PTSD and demonstrate that the dysregulated immune state of
 PTSD subjects parallels disease status.
Aim #2: Identify the heightened microglial-activating capacity of leukocytes of PTSD subjects.
Aim #3: Redirect inflammation-skewed blood leukocytes from subjects with PTSD to a balanced state.
Aim #4: Determine if redirecting the inflammation-skewed blood leukocytes of subjects with PTSD to a
 balanced state blocks their microglial-activating ability.
To limit the influence of variables, this study will involve a tightly-controlled and relatively homogeneous
population of Veterans, all with similar levels of combat exposure in the OEF/OIF arena, but some with PTSD
and others testing negative for PTSD. The proposed studies are expected to show immunological imbalance
toward an inflammatory phenotype in PTSD patients and that this imbalanced status stimulates microglial
inflammatory activity. Important for the goal of developing immunotherapeutic approaches for PTSD is
assessment of immune plastic...

## Key facts

- **NIH application ID:** 10828709
- **Project number:** 5I01CX001456-05
- **Recipient organization:** RALPH H JOHNSON VA MEDICAL CENTER
- **Principal Investigator:** ZHEWU WANG
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828709

## Citation

> US National Institutes of Health, RePORTER application 10828709, Dysregulated Immune State in PTSD Contributes to Microglial Inflammation (5I01CX001456-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10828709. Licensed CC0.

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