engleski

PTSD and immune reactivity ten years after the war- related trauma

General adaptation response to stress involves activation of adrenergic and hypothalamic- pituitary-adrenal systems (HPA) in order to achieve stability across an allostatic operating range. It is hypothesized that long-term effect of prolonged response to stress can result in substantial allostatic load with pathologic outcome. The biological consequences of stress have been extensively studied but inconsistent results regarding distinct hormonal and immune changes have been reported. The low cortisol level and increased number of glucocorticoid receptors (GCRs) is considered to be characteristic profile of HPA axis in patients with posttraumatic stress disorder (PTSD). These findings mainly rely on studies performed in Vietnam veterans, decades following exposure to trauma. In our previous research on war-related chronic stress we revealed a number of alterations in immune and hormonal systems in different groups of affected subjects. We tested PTSD patients in the more acute stage of illness (within 8 years from traumatic experience) and found decreased relative quantity of GCRs in lymphocytes and increased serum cortisol level. The reason for such a discrepancy could lie in a considerably shorter duration of allostatic load caused by adaptive response to stress. We assumed that more time is needed for reversal of hormone and its receptor expression to take place due to hyperactivity of HPA-axis. In line with this assumption our scope was to scrutinize another group of Croatian war veterans with chronic, combat-related PTSD ten years after the trauma. Immune response in 39 patient and 12 healthy controls was assessed by flow cytometric analysis of the main lymphocyte subsets, intracellular expression of Th1/Th2 cytokines, GCR and perforin in lymphocytes, and proinflamatory cytokine production in lipopolisaharide (LPS)-stimulated monocytes. NK cell activity was measured by 51Cr- release assays. Surprisingly, only B lymphocyte proportion was still elevated ten years after the trauma. There was no significant difference in either Th1/Th2 profile or level of proinflammatory cytokines between two groups. On the other hand, GCR level was increased while NK activity was decreased as compared to controls. Contrary to healthy controls, NK cells of PTSD patients had higher level of perforin than cytotoxic lymphocytes. These results sustain assumption of the exhaustive effect of allostatic load on immune response through enduring overactivity of HPA- axis. To further support this, we are now reassessing the group of PTSD patients already tested five years ago (more than ten years from traumatic experience). Preliminary results obtained so far in 18 of these patients and 10 controls are promising in this regard, particularly those concerning NK activity and GCR expression. Although not significantly different as compared to the first assessment, NK activity declines while GCR level tends to increase. We can conclude that changes in immune and endocrine system are not static in persons under prolonged stress but rather depend on duration of alostatic load and its impact on interactions involved in response to stress.

posttraumatic stress disorder; Th1/Th2 cytokines; NK activity; perforin; glukokorticoid receptors

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