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PTSD and Immune Dysregulation in Gulf War Veterans

Michael P. Everson, Susan Kotler, and Warren D. Blackburn, Jr.

Department of Veterans Affairs Medical Center, Birmingham, AL

The contributions of immunological abnormalities and post-traumatic stress disorder (PTSD) in Gulf War veteran (GWV) illnesses were studied. Many GWV patients complain of skin and joint problems, i.e., disorders which may have a common immunological basis. PTSD, an anxiety disorder associated with chronic stress, was diagnosed in approximately 10% of our study population which is in keeping with figures from the Vietnam era. Chronic stress is associated with physiological changes such as reduced capacity to resist disease, and one of the key body defenses against disease is the immune system. Recent work suggests that a dysregulated balance of cytokines produced by T helper (Th) cells of the immune system can play a significant role in the pathophysiologic sequelae of stress-related illnesses. The balance of Th1/Th2 cytokines is important in maintaining a balanced immune response of cell-mediated and humoral immunity against invading pathogens. Nonetheless, the effect of stress on this balance has not been adequately studied. In support of the notion that stress can indeed skew the balance of Th1 and Th2 cells and cytokines, acute surgical stress has been shown to alter cytokine patterns -- it induces a shift in the Th1/Th2 cytokine balance towards Th2, suggesting that cell-mediated immunity is down-regulated and antibody-mediated immunity is up-regulated after surgery. Although the mechanism by which this change in balance occurs is not clear, it may be secondary to stress-induced changes in hormones such as cortisol and catecholamines, both of which have been implicated in altering levels of cellular or humoral immunity.

Initial immune function studies compared randomly selected symptomatic GWVs (41 GWV subjects with or without PTSD) with 7 age- and sex-matched asymptomatic non-veteran controls, all of whom had received a tetanus toxoid (TT) vaccination within the last 5 years. We tested 2 doses of PHA and TT in proliferative cultures and recorded maximal stimulation index (SI) for each stimulant. Statistical comparisons using Fisher’s exact tests compared the incidence of SI greater than the value of the control mean SI. For PHA responses,, the data indicate that there is no statistical difference (p >0.6) between mitogen-induced cellular proliferation for symptomatic GWVs and asymptomatic controls, suggesting that the capacity for T lymphocytes to respond to non-specific signals is not impaired in symptomatic GWV patients. Conversely, when similar analyses were performed using a specific antigen (TT) as opposed to a non-specific mitogen (PHA), significant differences (p=0.017) were noted between the two groups. These data suggest that decreased cell-mediated immunity (as represented by decreased antigen-induced cellular proliferation) is associated with either the symptoms or physical presence of GWVs in the Persian Gulf area.

Our more recent data support a link between stress and immune dysfunction. Specifically, we compared immune responses of GWVs with a diagnosis of PTSD (subjects, n=3) with GWVs lacking such a diagnosis (controls, n=29). Proliferative responses to TT were normalized against PHA responses. When results were compared for suppressed responses to TT recall antigen using a 1-sided t-test, it was found that the response of PTSD subjects (0.222 ± 0.170) was statistically significantly suppressed (p <0.05) relative to normalized responses of controls (0.499 ± 0.475). These data suggest that cell-mediated immunity is decreased even further in GWVs with PTSD and that stress may play a role in some GWV illnesses.

KEYWORDS: PTSD, Stress, Cell-mediated Immunity

FUNDING SUPPORT: DoD-42 "The Symptomatic Persian Gulf Veterans Protocol: Ana Analysis of Risk Factors with an Immunologic And Neuropsychiatric Assessment"

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