Theoretical Accounts of Gulf War Syndrome: From Environmental Toxins to Psychoneuroimmunology and Neurodegeneration

Abstract

Non-specific illness includes a wide variety of symptoms: behavioural (e.g., reduced food and water intake), cognitive (e.g., memory and concentration problems) and physiological (e.g., fever). This paper reviews evidence suggesting that such symptoms can be explained more parsimoniously as a single symptom cluster than as a set of separate illnesses such as Gulf War Syndrome (GWS) and chronic fatigue syndrome (CFS). This superordinate syndrome could have its biological basis in the activity of pro-inflammatory cytokines (in particular interleukin-1: IL-1), that give rise to what has become known as the ‘sickness response’. It is further argued that the persistence of non-specific illness in chronic conditions like GWS may be (in part) attributable to a bio-associative mechanism (Ferguson and Cassaday, 1999). In the case of GWS, physiological challenges could have produced a non-specific sickness response that became associated with smells (e.g., petrol), coincidentally experienced in the Persian Gulf. On returning to the home environment, these same smells would act as associative triggers for the maintenance of (conditioned) sickness responses. Such associative mechanisms could be mediated through the hypothalamus and limbic system via vagal nerve innervation and would provide an explanation for the persistence of a set of symptoms (e.g., fever) that should normally be short lived and self-limiting. We also present evidence that the pattern of symptoms produced by the pro-inflammatory cytokines reflects a shift in immune system functioning towards a (T-helper-1) Th1 profile. This position contrasts with other immunological accounts of GWS that suggest that the immune system demonstrates a shift to a Th2 (allergy) profile. Evidence pertaining to these two contrasting positions is reviewed.

Cellular and humoral immune abnormalities in Gulf War veterans.

“…Furthermore, the presence of antibodies to MBP and striated and smooth muscle, increased immune complexes, and increased antibody titers to several DNA viruses indicate that viral reactivation and/or an active inflammatory immune process may be ongoing in some GWS patients (Ferguson andCassaday 2001/2001;Patarca 2001;Rook and Zumia 1997). Based on these observations and earlier reports by others, we believe that GWS is a multifactorial disease caused by exposure to a variety of environmental conditions, for example, xenobiotics, vaccinations, and other stressor-related conditions of the Gulf War environment as summarized in Figure 3.…”

“…Reported immunologic abnormalities suggest a shifting of the immune system to T H 1 and/or T H 2 profiles (Ferguson andCassaday 2001/2002;Patarca 2001;Rook and Zumia 1997;Zhang et al 1999). Moreover, levels of complement components (C3a, C4a, C5a) are significantly increased in chronic fatigue syndrome (CFS) patients versus controls (Sorensen et al 2003).…”

Cytokine profiles in human exposure to metals (IUPAC Technical Report)

“…This implies a key role of cytokines in both acute and chronic disease, and they are, therefore, also involved in immunological disorders arising from occupational and environmental exposure. Thus, there are many reports of the alteration of cytokines in, for example, allergies, hyper-reactive bronchial disorders, silicosis, and asbestosis, and furthermore in functional somatic syndromes such as fibromyalgia, chronic fatigue syndrome, Gulf War syndrome, multiple chemical hypersensitivity, sick building syndrome, etc., as well as in post-traumatic stress syndrome [5,12,13,17,[19][20][21][22][23][24][25][26][27][28][29]. However, alterations in cytokine expression pattern or concentrations are not specific for a defined agent or process, but rather reflect the reactivity of the organism to potential harm.…”

Non-termination of sickness behavior as precipitating factor for mental disorders

“…It is also known that cytokines can stimulate inflammatory pain and that Il-1 per se may lead to an increase in pain sensitivity in general [81]. Some authors reported increases in most of the pro-inflammatory cytokines (Il-1, Il-6, TNF-α) [70], [82], [83] and [84] but there are still many discrepancies in results. The picture with regard to the inflammatory cytokines in disorders with multiple subjective health complaints is, however, far from clear.…”