engleski

Interactions of immune and hormonal systems in combat- related posttraumatic stress disorder

General stress response includes activation of integrated neuroendocrine and immune systems. Bi-directional communication between two systems exist through common signalling molecules-neuropeptides, hormones and cytokines. Activation of immune cells can cause physiological, behavioural and affective changes (sickness) being on adaptive responses (1). Vice versa the influence of acute and chronic exposure to physical and/or psychological stress on immune system has been also established. Diverse phenomena related to stress, such as depression and suppression of specific immunity can be understood as a consequence of immune-brain pathways activation. Posttraumatic stress disorder (PTSD) is a condition which may develop after exposure to extreme traumatic experience accompanied by intense fear, helplessness or horror (natural disasters, traffic accidents, sexual abusing, war events). Diagnostic criteria for PTSD are described in DMS-IV (2). Extensive work on psychophysiological and neuroendocrine changes in PTSD has been undertaken (3) but these findings mainly rely on studies performed decades following exposure to trauma (Vietnam veterans or Holocaust survivors). Moreover, there is a few studies of immune status in PTSD sufferers. Our aim were to: a) evaluate the effect of combat-related PTSD on hormonal and immune responses few years after trauma exposure, b) to establish connections among the nervous, hormonal and immune systems, and c) to perform a follow up study of long-term effects of trauma responses as well as its impact on mental and physical health. We tested two combatant groups taking part in recent war in Croatia: 194 professional soldiers and 38 war veterans. Acording to “Croatian Stress Scale” (CROSS) (4.), professional soldiers were grouped as those without PTSD symptoms (score 0-7, N=52) and those with PTSD (score 8-35, N=142). In all studied war veterans PTSD was diagnosed acording to “Clinician-Administered PTSD Scale” (CAPS (5.)). Control group was made of 40 healthy, age and gender matched civilians. The number and proportions of total lymphocytes, the main lymphocyte populations (T, B, NK cells), as well as subpopulations expressing activation or memory markers were determined by immunophenotyping. In addition war veterans group, the level of intracellular glucocorticoid receptor (GCR) in lymphocytes was determinate by flow cytometry. Evaluating GCRs level in the lymphocytes is useful in defining the functional disturbances of the hypothalamic-pituitary-adrenocotrical (HPA) axis. In vitro NK cytotoxic activity and polymorphonuclear phagocyte functions (ingestion and digestion) were tested in all particpants. Serum level of proinflammatory cytokines (TNF-a, IL-1b, IL-6) and hormones (cortisol, prolactin, T3 and T4) were analised. An impact of combat-associated trauma exposure on immune and hormonal parameters was determuned in both combatant groups. The main dectected enumerative immune changes were increased number of B and total memory lymphocytes, increased percentage of B, T and memory TH cells as well as decreased number and percentage of NK cells. On the contrary, the activity of NK cells was increased. In both groups serum level of IL-6 was increased, but TNF-a level was increased only in the group of veterans. While in professional soldiers the level of T4 and T3 was increased, a cortisol and prolactin were increased in veterans. Relative quantity of lymphocyte´s GCRs in veterans was decreased. This GCRs downregulation in lymphocytes indicate a negative feedback response to increased cortisol level. The long-lasting overactivity of the HPA axis may result in allostatic load leading to alterations of HPA function (6). It has been shown that PTSD patients, decades after traumatic experience, are characterised by reduced cortisol level and increased number of GCRs (7). The main reason for only partial accordance in results of trauma survivors, may be due to differences on their psychosocial environement (more war veterans were unemployd and divorsed), age and/or time-cours aftertrauma experience. As there were minor differences between profesional soldiers with and without PTSD (increased percentage of memory TH-lymphocyte and the level of T3 hormone) we can conclude that observed alterations are more related to trauma then to PTSD itself, at least a few years after traumatic experience. 1. Ader R, Cohen N, Felten D (1995) Psychoneuroimmunology: interactions between the nervous system and the immune system. Lancet 345: 99-103. 2. American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, IV Ed. Washington, DC, American Psychiatric Press 3. Newport DJ, Nemeroff CB (2000) Neurobiology of posttraumatic stress disorder. Curre. Opin. Neurobiology 10:211-8. 4.Komar Z, Filjak T, Štefan S, Tišlarić G: Psychometric validation of Croatian Stress Scalle for psychological war consequences. U. The 1st international conference on psychosocial consequences of war. Dubrovnik: World veterans federation; 1998, pp 39 5. Blake DD, Weathers FW, Nagy LN, Kaloupek DG, Klauminzer G, Charney DS, Keane TM (1990) A clinician rating scale for assessing current and lifetime PTSD: the CAPS-1. Behav Ther 18: 187-188 6.McEwen BS (1998) Protective and Damaging Effects of Stress Mediators. N Engl J Med 338: 171-179 7. Yehuda R, Boisoneau D, Lowy MT, Giller EL Jr. Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without posttraumatic stress disorder. Arch Gen Psychiatry 1995;52:583-93

PTSP; ratni stres; imunosustav; hormoni

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