Gulf War illness: an overview of events, most prevalent health outcomes, exposures, and clues as to pathogenesis

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction:</jats:title><jats:p>During or very soon after the 1990–1991 Persian Gulf War, veterans of the conflict began to report symptoms of illness. Common complaints included combinations of cognitive difficulties, fatigue, myalgia, rashes, dyspnea, insomnia, gastrointestinal symptoms and sensitivity to odors. Gradually in the USA, and later in the UK, France, Canada, Denmark and Australia, governments implemented medical assessment programs and epidemiologic studies to determine the scope of what was popularly referred to as “the Gulf War syndrome”. Attention was drawn to numerous potentially toxic deployment-related exposures that appeared to vary by country of deployment, by location within the theater, by unit, and by personal job types. Identifying a single toxicant cause was considered unlikely and it was recognized that outcomes were influenced by genetic variability in xenobiotic metabolism.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>Derived from primary papers and key reports by the Research Advisory Committee on Gulf War Veterans’ Illnesses and the Institute of Medicine, a brief overview is presented of war related events, symptoms and diagnostic criteria for Gulf War illness (GWV), some international differences, the various war-related exposures and key epidemiologic studies. Possible exposure interactions and pathophysiologic mechanisms are discussed.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>Exposures to pyridostigmine bromide, pesticides, sarin and mustard gas or combinations thereof were most associated with GWI, especially in some genotype subgroups. The resultant oxidant stress and background exposome must be assumed to have played a role.</jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p>Gulf War (GW) exposures and their potential toxic effects should be considered in the context of the human genome, the human exposome and resultant oxidant stress to better characterize this unique environmentally-linked illness and, ultimately, provide a rationale for more effective interventions and future prevention efforts.</jats:p></jats:sec>

Lack of TRPM5-Expressing Microvillous Cells in Mouse Main Olfactory Epithelium Leads to Impaired Odor-Evoked Responses and Olfactory-Guided Behavior in a Challenging Chemical Environment

“…Chronic and severe chemical exposure is known to induce rhinitis, olfactory dysfunction, and other respiratory illnesses (Doty and Mishra, 2001; Kerr, 2015), which may be because such conditions likely overpower the ability of TRPM5-MCs to maintain MOE function. Therefore, our intention for this study was to choose chemical exposure conditions, to the best of our knowledge, that would challenge but not overwhelm the MOE’s ability to maintain its integrity so that we could evaluate the role of TRPM5-MCs in epithelial maintenance.…”

Detection of Serum microRNAs From Department of Defense Serum Repository

“…bronchiolitis, other cardiopulmonary illnesses, and even certain types of cancers later in life. 31–33 In this pilot study, we used 30 serum samples from the DoDSR that lack any identifier information to show the feasibility of using small amounts of serum to discover the presence of biomarkers and their associations with other constituents including cytokines, miRNAs, and PAHs in the serum. We show that the DoDSR serum samples were not affected by hemolysis and that we could detect a large number of putative biomarkers, including miRNAs, cotinine status, cytokines, chemokines, and PAHs within the same sample.…”

Long-term epigenetic alterations in a rat model of Gulf War Illness

“…After 25 years, GWI remains a complex, untreatable illness for up to 250,000 veterans of the 1990-1991 Persian Gulf War, with cognitive dysfunction and mood deficits being among the most prevalent and debilitating symptoms. Although the etiology of GWI is unknown, epidemiological investigations and experimental studies using animal models have determined that these impairments are causally related to neurotoxic chemical exposures such as PB, permethrin, and DEET encountered during deployment (RAC 2008(RAC , 2014Steele et al, 2012;Kerr, 2015;White et al, 2016). The current study provides novel evidence that combined exposure to low doses of GW-related chemicals and mild stress for 28 days causes epigenetic modifications in the brain that persist one year after exposure, including increased expression of miR-124-3p and miR-29b-3p in the hippocampus and regional alterations in global DNA methylation and DNA hydroxymethylation.…”

“…While several etiologies have been proposed for GWI, epidemiological studies have consistently identified exposure to cholinesterase-inhibiting chemicals during deployment to be among the strongest risk factors for the persistent symptoms affecting GW veterans (RAC, 2008(RAC, , 2014Steele et al, 2012;Kerr, 2015;White et al, 2016). These include the ingestion of pyridostigmine bromide (PB) pills issued as a prophylactic treatment against nerve agent attack and the overuse of insect repellants and pesticides such as DEET (N,N-diethyl-3methylbenzamide) and permethrin.…”

“…Although rodent models of GWI have revealed delayed and persistent effects on cognition, synaptic transmission, axonal transport, and alterations in genomic, proteomic, lipidomic, and metabolomic profiles, the effects of epigenetic modifications in the pathobiology of GWI have yet to be explored (Kerr, 2015;White et al, 2016). A major US report updated in 2014 recommended that research using animal models of GWI should "continue to examine the immediate, delayed, and persistent effects of acute exposures to chemicals and chemical mixtures" and advocated "epigenetic and genetic approaches to research" (RAC, 2014).…”