engleski

The effect of time on immune and endocrine parameters in PTSD: preliminary observations

The stress response can be a study model for neuroendocrine-immune interactions. Distinct profile of hypothalamic-pituitary-adrenocortical (HPA) axis, manifested by low cortisol level and increased number of glucocorticoid receptors (GR), is considered to be characteristic of posttraumatic stress disorder (PTSD). The findings mainly rely on studies performed in Vietnam veterans, decades following exposure to trauma. Investigation of immune status in PTSD survivors has been scarce and has shown heterogeneous results. Our previous study performed during the more acute stage of illness (within 8 years from traumatic event), revealed elevated plasma cortisol level and lower GR expression in each of the lymphocyte populations examined. 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. Therefore, we evaluated the effect of combat-associated traumatic experience on hormonal and immune responses in Croatian war veterans with PTSD diagnosed according to DSM-IV criteria within 8 years after traumatic event and re-assessed the same parameters 5 years later (more than 10 years from traumatic event) in 18 of the same PTSD patients and 10 age matched civilian controls. Proportions of total T (CD3), B (CD20) and natural killer (CD16, 56) cells, Th (CD3+CD4+) and Tc (CD3+CD8+) cells, activated B (CD20+CD23+), total (CD45RO) and Th (CD4+CD45RO+) memory lymphocyte subpopulations, as well as glucocorticoid receptor expression in these populations were determined by flow cytometry. NK cell activity was measured by 51Cr-release assays. At the first assessment, percentages of total T, Th, and memory Th cells were higher in PTSD patients than in healthy volunteers, without significant changes in patients 5 years later. On the other hand, after 5 years, PTSD patients had lower percentages of Tc and total memory cells compared with the first evaluation. While we observed elevated natural killer cell cytotoxicity compared to the healthy volunteers at the first examination, there were no significant changes in NK activity 5 years later. Furthermore, first examination showed the lower expression of GR in CD3, CD20 and CD16, 56 in PTSD patients than in healthy volunteers. Repeated measurement five years later did not sustain this difference, although its expression showed a tendency to increase in PTSD patients. Although our findings did not reveal significant difference in GCR expression in this preliminary follow up study, more reliable conclusions will be achieved after we assess all the subjects. Besides, decrease in percentages of some lymphocyte populations suggests an important effect of time on leukocyte trafficking, particularly on effector (CD8) and memory (CD45RO) cells, with potential implications for immune status in PTSD patients. 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.

PTSD; glucocorticoid receptors; HPA; cortisol; immune status

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