Fundamental mechanisms underlying the ill health and chronic fatigue syndrome suffered by atomic and gulf war veterans: A unifying hypothesis

Abstract

Atomic and Gulf War veterans often complain of an ill assorted collection of symptoms which are very like those experienced by those suffering from CFIDS (chronic fatigue and immune dysfunction syndrome) or ME (Myalgic Encephalomyelitis). There are two major hypotheses concerning the aetiology of Atomic and Gulf War Veterans ill health and CFIDS. The first suggests that CFIDS results from activation of a chronic stress response, which can be triggered by exposure to a variety of stress-inducing chemical or physical agents. These include radioisotopes and chemical pollutants and natural toxins. This pathway is thought to involve ion-gated channels, which lead to activation of H-Ras and MAPK pathways in affected individuals. The downstream consequences are mitochondrial dysfunction leading to the fatigue and chronic ill health. The other major idea is that the immune system is a major target leading to chronic ill health and other symptoms. Our suggestion is that both hypotheses are correct and that chronic exposure to stressors leads to genomic instability (GI), which is driven by stress signalling pathways. The GI particularly affects stem cells such as those in the bone marrow, brain and gastrointestinal tract, leading to the characteristic CFIDS symptoms, which result from compromise of immune system, digestive system and neural system function. Our key recommendation for new research in this area is to determine the mechanism by which stressed cells activate stress signalling and consequent GI. The key therapeutic emphasis should be to determine early intervention points in the pathway, which could prevent or reverse the stress signalling leading to alleviation of signal driven symptoms of CFIDS.