A Neuroimmune Model of Gulf War Illness

: Several studies have implicated immune system disruption in the pathophysiology of GWI. In addition, alterations in brain structure and functioning have been associated with specific exposures in theater, including pyridostigmine bromide and nerve gas agents. Recent studies conducted up to 25 years after the 1991 conflict have examined factors associated with the continuation or worsening of GWI. Drawing upon published studies of neural and immune system abnormalities in veterans with GWI, this paper proposes a model of GWI that takes into account neurologic and immunologic pathways, neuroimmune mechanisms of disease pathophysiology, individual predisposition due to sex and genetic background, and comorbid factors including neurological conditions such as neuritis/neuralgia and epilepsy that may occur along a continuum with GWI. The proposed neuroimmune model of GWI is likely to be useful for designing new research studies, clarifying factors involved in the continuation or worsening of GWI, and identifying biomarker screening algorithms for the illness. The proposed model goes beyond previously proposed frameworks for GWI by taking into account potential differences in risk based upon female vs. male sex, time elapsed since exposure to neurotoxicants, duration and severity of illness, comorbid conditions, and genotype.