Abstract
Between 25% and 30% of the nearly one million military personnel who participated in the 1991 Persian Gulf War became ill with chronic symptoms ranging from gastrointestinal to nervous system dysfunction. This disorder is now referred to as Gulf War Illness (GWI) and the underlying pathophysiology has been linked to exposure-based neuroinflammation caused by organophosphorous (OP) compounds coupled with high circulating glucocorticoids. In a mouse model of GWI we developed, corticosterone was shown to act synergistically with an OP (diisopropylflurophosphate) to dramatically increase proinflammatory cytokine gene expression in the brain. Because not all Gulf War participants became sick, the question arises as to whether differential genetic constitution might underlie individual differences in susceptibility. To address this question of genetic liability, we tested the impact of OP and glucocorticoid exposure in a genetic reference population of 30 inbred mouse strains. We also studied both sexes. The results showed wide differences among strains and overall that females were less sensitive to the combined treatment than males. Furthermore, we identified one OP-glucocorticoid locus and nominated a candidate gene—Spon1—that may underlie the marked differences in response.
Highlights
In 1991 the USA sent about 700,000 military personnel, joined by another 200,000 from allied nations, to the Persian Gulf to counter the invasion of Kuwait by Iraq
Average consumption of CORT added to the drinking water over the seven days varied widely (Figure 1)
We evaluated the effect of variability in corticosterone consumption on expression of the three cytokines by conducting analysis of covariance and reporting the adjusted means
Summary
In 1991 the USA sent about 700,000 military personnel, joined by another 200,000 from allied nations, to the Persian Gulf to counter the invasion of Kuwait by Iraq. Of those who participated in the conflict, 25–30% developed a multi-symptom malaise, Gulf War illness GWI [1,2]. The leading suspected causes are chemicals to which the personnel were exposed. These include depleted uranium, cholinesterase inhibitors used as insecticides or as prophylactics against nerve agents (e.g., chlorpyrifos and pyridostigmine bromide) and even
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