title: Telomere shortening and immune activity in war veterans with posttraumatic stress disorder.
abstract: BACKGROUND
  There is increasing evidence that chronic stress accelerates telomere erosion in leukocytes/peripheral blood mononuclear cells (PBMCs). However, functional changes associated with telomere shortening are poorly understood. We hypothesized that war veterans with PTSD would have shorter telomeres in PBMCs and that these cells might exhibit changes in measures of immune reactivity such as proliferation, cytokine production and expression of regulators of immune responses.
  
  
  METHODS
  We measured relative telomere length and basal telomerase activity in PBMCs of 62 individuals (PTSD patients (N=30); age-matched healthy controls (N=17), elderly volunteers (N=15)). In parallel, we have assessed proliferation of activated T cells, interferon (IFN)-γ, interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)-α and IL-6 cytokine production and expression of programmed death 1 (PD-1) receptor and its ligand PD-L1 on activated T cells.
  
  
  RESULTS
  Middle-aged war veterans with current PTSD had shorter PBMC telomere length than their age-matched healthy controls while the elderly had the shortest telomeres. There was no difference in telomerase activity between PTSD patients and healthy controls while telomerase activity was significantly lower in the elderly. While the elderly group exhibited robust changes in immune activity such as increased production of proinflammatory cytokines (TNF-α, IL-6) and reduced proliferation of all T cells, the PTSD group showed reduced proliferative response of CD8(+) T cells to high concentrations of mitogen and reduced spontaneous production of IL-2 and IFN-γ.
  
  
  CONCLUSIONS
  This study adds to the accumulating evidence that psychological trauma and chronic stress are associated with accelerated telomere attrition. However, changes in immune function associated with stress-related telomere shortening are not well understood. Although much less pronounced in PTSD patients than in elderly persons, reduced proliferative responses of T cells accompanied by shorter telomeres might be a sign of early immunosenescence. Together with reduced production of Th1 cytokines, observed immune changes may contribute to health risks associated with PTSD.
authors: Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Zagreb, Croatia. Electronic address: mjergovi@unizg.hr.
authors: Mladen
authors: M
authors: Jergović
authors: Dr. Josip Benčević General Hospital, Slavonski Brod, Croatia.
authors: Marko
authors: M
authors: Tomičević
authors: Dubrava University Hospital, Zagreb, Croatia.
authors: Anđelko
authors: A
authors: Vidović
authors: Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Zagreb, Croatia.
authors: Krešo
authors: K
authors: Bendelja
authors: Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Zagreb, Croatia.
authors: Ana
authors: A
authors: Savić
authors: Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Zagreb, Croatia.
authors: Valerija
authors: V
authors: Vojvoda
authors: Dr. Josip Benčević General Hospital, Slavonski Brod, Croatia.
authors: Dijana
authors: D
authors: Rac
authors: Dr. Josip Benčević General Hospital, Slavonski Brod, Croatia.
authors: Davorka
authors: D
authors: Lovrić-Čavar
authors: Institute of Immunology, Department for Cellular Immunology, Zagreb, Croatia.
authors: Sabina
authors: S
authors: Rabatić
authors: Emory University, Department of Psychiatry & Behavioral Sciences, Atlanta, GA, USA.
authors: Tanja
authors: T
authors: Jovanovic
authors: Institute of Immunology, Department for Cellular Immunology, Zagreb, Croatia.
authors: Ante
authors: A
authors: Sabioncello
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000276:immunology*; D060890:B7-H1 Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D017523:Croatia; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D012044:Regression Analysis; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology; D019098:Telomerase / Q000378:metabolism; D059506:Telomere Shortening; D014728:Veterans; D014857:Warfare
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D019098:Telomerase
keywords: Immunity; Immunosenescence; Posttraumatic stress disorder; Telomeres