Faculty Articles
Gulf War Illness: Is there Lasting Damage to the Endocrine-immune Circuitry?
Document Type
Article
Publication Title
Systems Biomedicine
ISSN
2162-8149
Publication Date
3-23-2016
Abstract
We reported previously that the persistence of complex immune, endocrine and neurological symptoms that afflict up to one third of veterans from the 1990-91 Gulf War might be supported by a misdirected regulatory drive. Here we use a detailed model of immune signaling in concert with an overarching circuit model of known sex and stress hormone co-regulation to explore how the failure of regulatory elements may further establish a self-perpetuating imbalance that closely resembles Gulf War Illness (GWI). Defects to the model were imparted iteratively and the stable regulatory modes supported by these altered immune-endocrine circuits were identified using repeated simulation experiments. In each case the predicted homeostatic regimes were compared to experimental data collected in male GWI (n=20 ) and matched healthy veterans (n=22 ). We found that alignment of GWI with a new homeostatic regime improved significantly when cortisol's normal anti-inflammatory activity was interrupted. Alignment improved further when this cortisol insensitivity was compounded by the loss of the normal antagonistic effects of Th1 cytokines on Th2 lymphocyte activation. Together these simulation results suggest altered glucocorticoid gene regulation compounded by possible changes in IGF-1 regulation of Th1:Th2 immune balance may be key underlying features of GWI.
DOI
10.1080/21628130.2015.1127498
Volume
2
Issue
4
First Page
80
Last Page
89
NSUWorks Citation
Rice, M. A.,
Craddock, T. J.,
Folcik, V. A.,
del Rosario, R. M.,
Barnes, Z. M.,
Kilmas, N. G.,
Fletcher, M. A.,
Zysman, J. P.,
Broderick, G.
(2016). Gulf War Illness: Is there Lasting Damage to the Endocrine-immune Circuitry?. Systems Biomedicine, 2(4), 80-89.
Available at: https://nsuworks.nova.edu/cps_facarticles/1683
