Cellular Immune Activation in Gulf War Veterans

The etiology and pathology of illnesses related to the first Persian Gulf War are unclear. Among the constellation of symptoms noted in sick veterans, some, such as skin rashes, musculoskeletal pains, and neuropsychiatric problems, have been proposed to reflect an underlying immune dysfunction. In this study we explored the hypothesis that sickness following deployment to the Gulf in 1991 is associated with altered immune function, and we examine possible associated exposures. In particular, we focused on peripheral blood Th1/Th2 balance by measuring intracellular production of IFN-gamma, IL-2 (Th1), IL-4 (Th2), and IL-10 by CD4 T cells, using a nested case control study design within a large epidemiological survey. We compared symptomatic Gulf War veterans (sGWV) with well GWVs (wGWV), and a second control group of symptomatic veterans who served in Bosnia or were nondeployed military personnel of the same era. We found evidence for an altered immune status in sGWV in comparison to the other study groups. In particular, ongoing Th1-type immune activation was associated with multisymptom illness in GWVs, with sick veterans having significantly elevated levels of IFN-gamma and IL-2 producing CD4+ cells in the absence of in vitro stimulation compared with wGWVs (P = 0.01 and P =0.001). In vitro polyclonal activation revealed significantly elevated levels of IL-10 producing memory CD4 cells in sGWVs (P <0.001), but other cytokines were normal. In terms of possible exposures that might influence immune function, we found a trend for reduced levels of IFN-gamma producing cells after polyclonal activation with increasing numbers of vaccines administered (P <0.05) but no changes in other cytokines. These data show that multisymptom illness in Gulf War veterans is characterized by ongoing Th1-type immune activation and a biased generation of memory cells secreting the suppressor cytokine, IL-10.     

Environmental health concerns of the Persian Gulf War.

Environmental health concerns in the Persian Gulf are peculiar to the geography of the region. Prevention of heat and solar injury deserves primary consideration, but cold injury also may occur in the desert. Immunizations are recommended against a number of diseases, while malarial chemoprophylaxis is necessary in Iraq and Kuwait. In addition to malaria, other parasitic diseases deserve consideration. Diarrheal diseases, diseases from the desert dust, and products of infected desert animals are of concern. Additional natural hazards are venomous bites from scorpions and desert snakes. Finally, threats of enemy action necessitated protection from nuclear biological and chemical weapons and LASER eye/skin injury. Unexploded ordinance will constitute a continuing hazard into the future.     

Relationship of psychiatric status to Gulf War veterans' health problems.

OBJECTIVE: A growing body of research has shown that there are important links between certain psychiatric disorders and health symptom reporting. Two disorders in particular (posttraumatic stress disorder (PTSD) and major depression) have been the most widely implicated to date, and this association has sometimes been used to explain the occurrence of ill-defined medical problems and increased somatic symptoms in certain groups, most recently Gulf War veterans. METHODS: Structured psychiatric diagnostic interviews were used to examine the presence of major psychiatric (axis I) disorders and their relation to health symptom reporting in a well-characterized, stratified subset of Gulf War veterans and a non-Gulf-deployed veteran comparison group. RESULTS: Rates of most psychiatric disorders were substantially lower than national comorbidity estimates, consistent with prior studies showing heightened physical and emotional well-being among active-duty military personnel. Rates of PTSD and major depression, however, were significantly elevated relative to the veteran comparison group. The diagnosis of PTSD showed a small but significant association with increased health symptom reports. However, nearly two-thirds of Gulf participants reporting moderate to high health symptoms had no axis I psychiatric diagnosis. CONCLUSIONS: Results suggest that rates of psychiatric illness were generally low with the exception of PTSD and major depression. Although PTSD was associated with higher rates of reported health problems, this disorder did not entirely account for symptoms reported by participants. Factors other than psychiatric status may play a role in Gulf War health problems.     

No evidence for altered cellular immune functions in personnel deployed in the Persian Gulf during and after the Gulf War--The Danish Gulf War study

Veterans who have participated in the Gulf War suffer from a number of symptoms, collectively referred to as the Gulf War Syndrome. It has been hypothesized that a change in the systemic cytokine balance or other changes in immunological parameters could be responsible for some of the symptoms. We analyzed the peripheral blood natural killer (NK) cell activity of 686 Gulf War personnel who had been present in the Persian Gulf area during and immediately after the Gulf War as well as 231 gender and age-matched controls. The test material included individual samples of frozen peripheral blood mononuclear cells kept at -139 degrees C for a period of 50 to 380 days prior to NK cell analysis of freshly thawed cells. Significant differences in NK-cell activity were not observed by direct comparison of the levels of natural cytotoxic activity in the two groups. However, NK-cell cytotoxicity as such decreased due to cryopreservation. Surprisingly, the NK cells obtained from control donors were significantly (p<0.0001) more sensitive to freezing conditions than cells from the Gulf War personnel, leaving the marginal comparison between the two groups untrustworthy, in particular because of the marked difference between the -139 degrees C storage times used for the two groups. Freshly thawed samples of peripheral blood T lymphocytes (CD2+ cells) from 109 randomly selected Gulf War personnel and 68 gender- and age-matched controls were stimulated for 3 days with phytohemagglutinin followed by 4 h activation by phorbol ester and ionomycin, and were stained for intracellular content of interleukin-2, -5, -10 and interferon-gamma. As with natural cytotoxicity, the length of cell storage at -139 degrees C influenced the production of cytokines. No significant differences in the cytokine production between the two groups were observed when the influence of the storage period was taken into consideration. Together, these data suggest that no overall long-term effects on NK-cell function and T-cell cytokine production are present in the Danish Gulf War personnel. Moreover, cryopreservation is a major potential source of bias when studying the physiology of thawed NK and T cells.     

Changes in Immune Parameters Seen in Gulf War Veterans but Not in Civilians with Chronic Fatigue Syndrome

The purpose of this study was to evaluate immune function through the assessment of lymphocyte subpopulations (total T cells, major histocompatibility complex [MHC] I- and II-restricted T cells, B cells, NK cells, MHC II-restricted T-cell-derived naive and memory cells, and several MHC I-restricted T-cell activation markers) and the measurement of cytokine gene expression (interleukin 2 [IL-2], IL-4, IL-6, IL-10, IL-12, gamma interferon [IFN-γ], and tumor necrosis factor alpha [TNF-α]) from peripheral blood lymphocytes. Subjects included two groups of patients meeting published case definitions for chronic fatigue syndrome (CFS)—a group of veterans who developed their illness following their return home from participating in the Gulf War and a group of nonveterans who developed the illness sporadically. Case control comparison groups were comprised of healthy Gulf War veterans and nonveterans, respectively. We found no significant difference for any of the immune variables in the nonveteran population. In contrast, veterans with CFS had significantly more total T cells and MHC II⁺ T cells and a significantly higher percentage of these lymphocyte subpopulations, as well as a significantly lower percentage of NK cells, than the respective controls. In addition, veterans with CFS had significantly higher levels of IL-2, IL-10, IFN-γ, and TNF-α than the controls. These data do not support the hypothesis of immune dysfunction in the genesis of CFS for sporadic cases of CFS but do suggest that service in the Persian Gulf is associated with an altered immune status in veterans who returned with severe fatiguing illness.     

The problem of Gulf War syndrome

Following a war with widespread attention to and concern over the potential for numerous biological and chemical warfare exposures, some Gulf War veterans returned home and developed various illnesses. Although some of these illnesses are readily diagnosable, the so-called Gulf War syndrome has remained a controversial and nebulous diagnosis. It is characterized by multiple, subjective symptoms, and by a lack of objective pathology. To date, the search for a single disease entity and a biological model to explain this illness has been unsuccessful. Wars have long affected the health of veterans in multiple ways, and a single disease entity is not likely as a viable explanation for these outcomes. Given the nature of the illness, and its overlap with many other controversial chronic illnesses, we suggest that the biopsychosocial model may provide a better solution to this diagnostic conundrum.     

Neuropsychological correlates of Gulf War syndrome.

As part of a comprehensive multispecialty project, the present study reports on the neurocognitive and psychological function of veterans who report Persian Gulf War-related symptoms. The neuropsychological and psychological performances of 26 ill Gulf War veterans were compared to 20 well veterans from the same military unit. Neurocognitive functions assessed included intelligence, abstraction and problem-solving, attention and concentration, memory and learning, language and visual-spatial function, and sensorimotor abilities. Psychological function was measured by self-report questionnaires. Results indicated global and consistently poorer intellectual and neurocognitive function among the ill veterans compared to the control veterans. A generalized pattern of neuropsychological deficit was evident for the ill veterans. Psychological profiles of the ill veterans were similar to those in general medical patients. Based on these findings and results from the multispecialty investigation, we conclude that some of the ill veterans have experienced neurotoxic injury resulting in chronic neuropsychological impairment that is related to their service in the Persian Gulf War.     

Influence of pain anticipation on brain activity and pain perception in Gulf War Veterans with chronic musculoskeletal pain

Anticipation of a painful experience can influence brain activity and increase sensitivity to experimental somatosensory stimuli in healthy adults, but this response is poorly understood among individuals with chronic musculoskeletal pain (CMP). Studies of brain and perceptual responses to somatosensory stimuli are used to make inferences about central nervous system dysfunction as a potential mechanism of symptoms. As such, we sought to (a) determine the influence of pain anticipation on pain‐relevant brain regions and pain perception, and (b) characterize potential differences in these responses between Gulf War Veterans with CMP and matched healthy control (CO) Veterans. CMP (N = 30) and CO Veterans (N = 31) were randomized to conditions designed to generate expectations that either painful (pain) or nonpainful (no pain) stimuli would be administered. Brain responses to five nonpainful thermal stimuli were measured during fMRI, and each stimulus was rated for pain intensity and unpleasantness. In the pain condition, an incremental linear decrease in activity across stimuli was observed in the posterior cingulate cortex, cingulate cortex, and middle temporal gyrus. Further, in the pain condition, differential responses were observed between CMP and CO Veterans in the middle temporal gyrus. These findings indicate that brain responses to nonpainful thermal stimuli in Veterans with CMP are sensitive to pain anticipation, and we recommend accounting for the influence of pain anticipation in future investigations of central nervous system dysfunction in CMP.     

某部队官兵男性生殖健康情况的调查研究

目的了解部队男性官兵对生殖健康概念及内容的了解情况及其生殖系统体检情况。方法采用整群分层、随机抽样的方法,对某边疆部队300名官兵进行问卷调查,并对其生殖系统进行相关检查。结果对生殖健康概念及内容了解的约占66%,其中与被调查者的学历、职务、是否来自城市等因素有关;8%的人认为遗精可能会影响健康;10.7%的人认为自慰会影响健康;20%的人对性传播疾病的病种及传播途径了解不够;10%的人有包皮过长,其中做过手术者占2/3;5.3%的人有不同程度的精索静脉曲张;发现前列腺炎6例,均与已婚干部及入伍前有女朋友的战士有关。结论部队官兵对生殖健康概念及内容了解较好,但还应适当加强宣传教育;官兵生殖健康良好,最好定期进行生殖系统疾病检查。     

The ageing male reproductive tract

Ageing of the male reproductive system is characterized by changes in the endocrine system, hypogonadism, erectile dysfunction and proliferative disorders of the prostate gland. Stochastic damage accumulating within ageing leads to progressive dysregulation at each level of the hypothalamic-pituitary-gonadal (HPG) axis and in local auto/paracrine interactions, thereby inducing morphological changes in reproductive target organs, such as the prostate, testis and penis. Despite age-related changes in the HPG axis, endocrine functions are generally sufficient to maintain fertility in elderly men. Ageing of the male reproductive system can give rise to clinically relevant manifestations, such as benign prostatic hyperplasia (BPH), prostate cancer (PCa) and erectile dysfunction (ED). In this review, we discuss morphological/histological changes occurring in these organs and current views and concepts of the underlying pathology. Moreover, we emphasize the molecular/cellular pathways leading to reduced testicular/penile function and proliferative disorders of the prostate gland.     

Somatic symptoms in Gulf War mortuary workers

OBJECTIVE: The objective of this article is to examine the relationship between exposures to the dead and the development of somatic symptoms. METHODS: We studied the pre-post responses of 352 military men and women who worked in the mortuary that received the dead from the Persian Gulf War (Operation Desert Storm) in 1990 to 1991. Symptoms of somatization were measured before and after exposure to the dead. The respondents were volunteers and nonvolunteers for assignment to the mortuary; some had prior experience in handling the dead and some did not. Four groups of participants were examined based on the degree of exposure to remains. Age, sex, volunteer status, prior experience handling remains, and preexposure measures of depression and mutilation fear were statistically controlled. RESULTS: Postexposure somatic symptoms increased significantly over preexposure levels for the two groups with the most exposure to the dead. CONCLUSIONS: These results provide additional evidence that exposure to the dead is related to somatic distress.