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Stress:  Research Article

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Changes of Cytolytic Cells and Perforin Expression in Patients with Posttraumatic Stress Disorder

CITATION: Skarpa, I., Rubesa, G.,  Moro, L., Manestar, D., Petroveki, M., Rukavina, D. (2001).  Changes of Cytolytic Cells and Perforin Expression in Patients with Posttraumatic Stress Disorder.  Croatian Medical Journal 42(5):551-555.

ABSTRACT: 

Aim. To define phenotypic characteristics of cytotoxic T lymphocytes (CTL) and natural killer cells (NK) in peripheral blood, frequency of somatic symptoms, and level of anxiety and depression in 25 patients clinically diagnosed with chronic post-traumatic stress disorder (PTSD).

Methods. Patients were divided into two sub-groups according to the stressor: 18 PTSD patients with the battlefield experience and 7 PTSD patients with battlefield experience who were tortured as the prisoners of war (POW) in Bosnian-Serbian camps. The control group consisted of 15 healthy volunteers matched to the patients by sex and age. We tested all patients using Beck’s depression inventory, Spielberger anxiety test, and somatic disturbance list, and analyzed their peripheral blood lymphocytes using flow cytometry with the double fluorescence staining of cell surface antigens (CD3, CD4, CD8, CD16, and CD56) and intracellular cytolytic molecule perforin (P), a mediator of cytolytic action at the molecular level.

Results. All PTSD patients showed a significant level of anxiety, depression, and numerous somatic symptoms. The only significant difference between PTSD patients with and without POW experience was in the anxiety level (median, 71; range 61-79; vs median, 65; range, 49-77). PTSD patients with POW experience had significantly higher levels of CD16+ cells (median, 37%; range, 16-55%) than those without it (median, 12%; range, 5-37%). Double labeling for intracellular P antigen and cell surface antigens showed the highest levels of CD16+P+ (median, 33%; range, 15-40%; vs median, 10%; range, 3-29%) and CD56+P+ (median, 21%; range, 11-40%; vs median 8%; range, 1-30%) cells in PTSD-POW patients.

Conclusion. Chronic PTSD patients who survived concentration camps show the most numerous alterations in PBL phenotype, the highest number of perforin-containing cells, and a significantly higher level of anxiety.

References

1 Dekaris D, Sabioncello A, Rabatid S, Svoboda-Beusan I, Ruptid Ratunica N, Tomas"id J. Multiple changes of immunologic parameters in prisoners of war. Assessments after release from a camp in Manjata, Bosnia. JAMA 1993;270:595-9.

2 Sabioncello A, Kocijan-Hercigonja D, Rabatid S, Tomas"id J, Jeren T, Matijevid Lj, et al. Immune, endocrine and psychological responses in civilians displaced by war. Psychosom Med 2000;62:502-8.

3 American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington (DC): American Psychiatric Association; 1994.

4 Gorst-Unsworth C, Goldenberg E. Trauma-related factors compared with social factors in exile. Psychological sequelae of torture and organized violence suffered by refugees from Iraq. Br J Psychiatry 1998;172:90-4.

5 Kozarid-Kovatid D, Hercigonja DK, Grubis"id-Ilid M. Posttraumatic stress disorder and depression in soldiers with combat experiences. Croat Med J 2001;42: 165-70.

6 Brady KT, Killeen TK, Brewerton T, Lucerini S. Comorbidity of psychiatric disorders and posttraumatic stress disorder. J Clin Psychiatry 2000;61:22-32.

7 Rontevid-Grieta I, Frantis"kovid T, Moro Lj, Kas"telan A. Depression and torture. Mil Med 2001;166:530-3.

8 Shresta NM, Sharma B, Van Ommeren M, Regmi S, Makaju R, Komproe I, et al. Impact of torture on refugees displaced within the developing world; symptomatology among Bhutanese refugees in Nepal. JAMA 1998;280:443-8.

9 Shalev AY, Freedman S, Peri T, Brandes D, Sahar T, Orr SP, et al. Prospective study of posttraumatic stress disorder and depression following trauma. Am J Psychiatry 1998;155:630-7.

10 Yehuda R, Siever LJ, Teicher MH, Levengood RA, Gerber DK, Schmeidler J, et al. Plasma norepinephrine
and 3-metoxy-4-hydroxypheyglycol concentrations and severity of depression in combat posttraumatic stress disorder and major depressive disorder. Biol Psychiatry 1998;44:56-63.

11 Selye H. History of the stress concept. In: Goldberg L, Breznitz S, editors. Handbook of stress. New York (NY): The Free Press; 1993. p. 7-17.

12 Khansari DN, Murgo AJ, Faith RE. Effects of stress on the immune system. Immunol Today 1990;11:170-5.

13 O’Leary A. Stress, emotion, and human immune function. Psychol Bull 1990;108:363-82.

14 Podack ER. Functional significance of two cytolytic pathways of cytotoxic T lymphocytes. J Leukoc Biol
1995;57:548-52.

15 Podack ER. Execution and suicide: cytotoxic lymphocytes enforce Draconian laws trough separate molecular pathways. Curr Opin Immunol 1995;7:11-6.

16 Kagi D, Seiler P, Pavlovid J, Ledermann B, Burki K, Zinkernagel RM, et al. The roles of perforin- and Fas-dependent cytotoxicity in protection against cytopathic and noncytopathic viruses. Eur J Immunol 1995;25: 3256-62.

17 Spielberger CD, Gorsuch RL, Lushene RE. STAI Manual for the state–trait anxiety inventory. Palo Alto (CA): Consulting Psychology Press; 1970.

18 Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psych 1961;4:561-71.

19 Rukavina D, Rubesa G, Gudelj L, Haller H, Podack ER. Characteristics of perforin expressing lymphocytes within the first trimester decidual of human pregnancy. Am J Reprod Immunol 1995;33:394-404.

20 Hameed A, Olsen KJ, Cheng L, Fox WM III, Hruban RH, Podack ER. Immunohistochemical identification of cytotoxic lymphocytes using human perforin monoclonal antibody. Am J Pathol 1992;140:1025-30.

21 Rukavina D, Rubesa G, Gudelj L, Podack ER. Human decidual lymphocytes: phenotype, perforin expression and function. Reg Immunol 1994;6:320-5.

22 Rukavina D, Laskarin G, Rubesa G, ~trbo N, Bedenicki I, Manestar D, et al. Age-related decline of perforin expression in human cytotoxic T lymphocytes and natural killer cells. Blood 1998;92:2410-20.