Modeling Neuroimmune Interactions in Human Subjects and Animal Models to Predict Subtype Specific Multidrug Treatments for Gulf War Illness

Introduction

Gulf War Illness (GWI) is a persistent chronic neuroinflammatory illness exacerbated by external stressors and characterized by fatigue, musculoskeletal pain, cognitive and neurological problems linked to underlying immunological dysfunction for which there is no known treatment.  Here, we constructed a logic model of immune regulatory behavior between human clinical samples and mouse models of GWI subtyped by exposure to traumatic stress.  We identify several ideal multi-intervention strategies and potential drug candidates that may be used to treat chronic neuroinflammation in GWI.

Data Collection Methods

Adult male C57BL/6J mice received a chronic exposure to corticosterone (CORT) at levels mimicking high physiological stress followed by exposure to the sarin surrogate, diisopropyl fluorophosphate (DFP).  These mice were then re-exposed to CORT every other week for a total of eleven weeks, followed by a systemic immune challenge with lipopolysaccharide (LPS).  The neuroinflammatory effects were interrogated by analysis of cytokine mRNA expression.

Publications using this dataset

Arias FJC, Aenlle K, Abreu M, Holschack MA, Michalovicz LT, Kelly KA, Klimas N, O’Callaghan JP, Craddock TJA: Modeling neuroimmune interactions in human subjects and animal models to predict subtype specific multidrug treatments for Gulf War Illness. International Journal of Molecular Sciences 2021, 22, 8546. https://doi.org/10.3390/ijms22168546.

Acknowledgements

The work that generated this dataset was supported by the National Institute for Occupational Safety and Health and a Congressionally-Directed Medical Research Program, Gulf War Illness Research Program grants (W81XWH-16-1-0632 (Craddock PI), and W81XWH-16-1-0552 (Craddock PI), W81XWH-13-2-0085 (Morris PI)).

When a publication makes use of this dataset, acknowledgement of the development of the dataset should be attributed to the NIOSH Health Effects Laboratory Division.

We would also like to recognize the work of Michalovicz LT, Kelly KA, and O’Callaghan JP.

Contact

NIOSH/Health Effects Laboratory Division
Toxicology and Molecular Biology Branch
(304) 285-6272