| Abstract | Posttraumatski stresni poremećaj (PTSP) vezan je uz povećanu pojavnost tjelesnih, osobito autoimunosnih i kardiovaskularnih bolesti. Smatra se da su stresom uvjetovane promjene endokrinog i imunosustava ključni posrednici u razvoju ovih bolesti. Unatoč opsežnom istraživanju u ovom području, ne postoje jasni dokazi o specifičnim promjenama imunosustava i endokrinog sustava u PTSP-u. Postoje naznake da bi ove promjene mogle ovisiti o trajanju PTSP-a. Cilj naše studije bio je ispitati mijenjaju li se razine hormona (kortizol i prolaktin), citokina (interleukin-6 (IL-6) i faktor nekroze tumora α (TNF-α)), ekspresija glukokortikoidnog receptora (GR) u pojedinim limfocitnim subpopulacijama, funkcija imunosustava (citotoksičnost urođenoubilačkih (NK, engl. natural killer) stanica) i udio raznih subpopulacija limfocita (T-limfociti, pomoćnićki i citotoksični T-limfociti, Blimfociti, NK-stanice, ukupni i pomoćnićki memorijski T-limfociti) tijekom vremena u osoba s PTSPom. Također smo željeli ispitati međudjelovanje gore navedenih varijabli kao i njihov odnos prema razini simptoma PTSP-a. Ispitali smo 39 hrvatskih ratnih veterana s dijagnozom PTSP-a i 37 (25 u drugom ispitivanju) po spolu i dobi ujednačenih zdravih dobrovoljaca u dvije vremenske točke u razmaku od 5,6 godina (medijan; interkvartilni raspon: 5,4-6,3). Koncentracija hormona u serumu određena je radioimunotestom, a koncentracija citokina imunoenzimskim testovima. Funkcija imunosustava procijenjena je testom citotoksičnosti NK-stanica prema tumorskim K562 ciljnim stanicama obilježenim s 51Cr. Ukupni broj limfocita, udio pojedinih subpopulacija limfocita i ekspresija GR-a u tim stanicama određena je metodom protočne citometrije. U prvoj vremenskoj točki osobe s PTSP-om imale su povišenu koncentraciju kortizola, prolaktina i TNF-α u serumu, povišenu citotoksičnost NK-stanica, povećan ukupni broj cirkulirajućih limfocita, povišen udio T-limfocita, pomoćnićkih T-limfocita, ukupnih memorijskih i pomoćnićkih memorijskih T-limfocita dok je ekspresija glukokortikoidnog receptora bila snižena u svim subpopulacijama limfocita u odnosu na zdrave kontrole. U drugoj vremenskoj točki samo su koncentracija prolaktina i ukupni broj limfocita ostali povišeni dok u drugim varijablama nije bilo razlike u odnosu na zdrave kontrole. Možemo zaključiti da promjene endokrinog i imunosustava nisu statične u osoba s PTSP-o, već vjerojatno ovise o trajanju alostatskog opterećenja koje je uvjetovano samim stresnim poremećajem i njegovim utjecajem na međudjelovanje kompoenti endokrinog i imunosustava uključenih u stresnu reakciju. |
| Abstract (english) | Posttraumatic stress disorder (PTSD) has been associated with increased medical morbidity, particularly with the autoimmune and cardiovascular diseases. It is assumed that stress-related changes in the endocrine and immune systems are key mediators involved in the development of diseases. Despite extensive research in the field, there is no conclusive evidence linking specific changes in the endocrine and immune systems to PTSD. Some evidence suggests that those changes might be realated to the duration od the PTSD. The aim of our study was to investigate weather hormones (cortisol and prolactin), proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)), lymphocyte expression of glucocorticoid receptor (GR), immune function (NKCC, natural killer cell cytotoxicity) and peripheral blood percentages of various lymphocyte subpopulations (T cells, helper T cells, cytotoxic T cells, B cells, natural killer (NK) cells, memory T cells and memory helper T cells) change in patients with PTSD over time. We also wanted to investigate mutual interactions of above mentioned variables and their relation to PTSD symptoms. We assessed 39 Croatian war veterans with PTSD and 37 (25 in the second time point) sex and age matched healthy volunteers in two time points separated by 5.6 years (median; interquartile range: 5.4-6.3). Hormones were measured by radioimmunoassay and cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Immune function was assessed with the in vitro natural killer cell cytotoxicity (NKCC) toward 51Cr-labeled K562 target cells. Lymphocyte counts, immunophenotye and intracellular glucocorticoid receptor expression were determined by threecolor flow cytometry. In the first time point serum levels of cortisol, prolactin, and TNF-α, NKCC, lymphocyte count, total T cells, helper T cells, total memory cells, and helper memory T cells were increased, while glucocorticoid receptor expression was decreased in all lymphocyte subpopulations in PTSD patients compared to controls. In the second time point only prolactin levels and lymphocyte counts remained elevated and no significant differences in other variables have been observed. We can conclude that changes in the endocrine and immune systems are not static in persons with PTSD but rather depend on duration of alostatic load posed by the disorder and its impact on interactions between endocrine and immune systems involved in stress response. |
