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ARTICLE |

Multiple Changes of Immunologic Parameters in Prisoners of War: Title and subTitle BreakAssessments After Release From a Camp in Manjača, Bosnia FREE

Dragan Dekaris, MD, PhD; Ante Sabioncello, PhD; Renata Mažuran, PhD; Sabina Rabatić, PhD; Ivna Svoboda-Beusan, PhD; Nives Ljubić Računica, MD; Jelka Tomašić, PhD
[+] Author Affiliations

Reprint requests to Institute of Immunology, Rockefellerova 10, 41000 Zagreb, Croatia (Dr Dekaris).


JAMA. 1993;270(5):595-599. doi:10.1001/jama.1993.03510050061028
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Objective.  —To assess immune reactivity in men just released from a war prisoner camp.

Participants.  —Random sample of 29 men from a group of 764 liberated detainees in war prisoner camp in Bosnia, 15 matched healthy control subjects, and prewar historical control subjects.

Main Outcome Measures.  —Report on immune reactivity parameters, such as lymphocyte immunophenotypes, natural killer cell and phagocyte function, serum cytokines, and hormones.

Results.  —Compared with control subjects, detainees had significantly lowered red blood cell count, hemoglobin mass concentration, hematocrit, total serum proteins, and albumin level, while the percentage and count of monocytes and nonsegmented neutrophils were increased. Flow cytometry revealed a significant increase in percentage of activated lymphocytes, activated T lymphocytes, Tc/s lymphocytes, B lymphocytes, and total HLA-DR lymphocytes. The absolute counts of activated lymphocytes and activated T lymphocytes were also significantly increased. The percentages of naive Th/i lymphocytes and the ratio of CD4:CD8 lymphocytes were decreased. The in vitro natural killer cell cytotoxic activity and phagocytic functions of ingestion and digestion were significantly depressed. Serum interferon, serum cortisol, and prolactin were also significantly lowered. Serum tumor necrosis factor was increased.

Conclusions.  —Alterations in the main parameters of the immune system and depression of important immune effector functions may have resulted from the psychological stress, physical deprivation, and malnutrition experienced by these war camp prisoners during their detainment.(JAMA. 1993;270:595-599)

REFERENCES

Chrousos GP, Gold PW.  The concepts of stress and stress system disorders. JAMA . 1992;;267:1244-1252.
Khansari DN, Murgo AJ, Faith RE.  Effects of stress on the immune system. Immunol Today . 1990;;11:170-175.
O'Leary A.  Stress, emotion, and human immune function. Psychol Bull . 1990;;108:363-382.
Serban G.  Stress in affective disorders. Methods Achiev Exp Pathol . 1991;;15:200-220.
Kiecolt-Glaser JK, Glaser R.  Stress and immune function in humans.  In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology . Orlando, Fla: Academic Press Inc; 1991;:849-867.
Ballieux RE.  Impact of mental stress on the immune response. J Clin Periodontol . 1991;;18:427-430.
Bentdal ØH, Frøland SS, Djøseland O.  Alterations in serum cortisol, CD4+/CD8+ lymphocyte sub-population ration and T cell mediated suppression of immune responses in the malnutrition of anorexia nervosa. Clin Nutr . 1991;;10;167-172.
Chandra RK.  1990 McCollun Award Lecture: nutrition and immunity: lessons from the past and new insights into the future. Am J Clin Nutr . 1991;; 53:1087-1101.
Chandra RK.  Protein-energy malnutrition and immunological responses. J Nutr . 1992;;122:597-600.
Law DK, Dudrick SJ, Abdou NI.  Immunocompetence of patients with protein-calorie. Ann Intern Med . 1973;;79:545-550.
Redmond HP, Shou J, Kelly CJ, et al.  Immunosuppressive mechanisms in protein-calorie malnutrition. Surgery . 1991;;110:311-317.
Mazowiecki T.  Report of special rapporteur of the Commission on Human Rights on the situation of human rights in the territory of former Yugoslavia.  In: Report to the General Assembly of the UN . New York, NY: United Nations; 1992;:18-19. 47th General Assembly Session, agenda item 98c.
Novotny Z.  Manjača: how the Yugoslav Federal Army treats the prisoners. Croatian Med J . 1992;;(war (suppl 2) ):90-92.
Borc̆ić D, Kuzman I, Bobinac E, Beus I, Schoen wald S.  Medical status of prisoners of war from Manjača and Glina camp. Croatian Med J . 1992;; (war (suppl 2) ):93-96.
DeZan D, Anić N, Klein E.  Psychic status of the Manjača camp prisoners. Croatian Med J . 1992;; (war (suppl 2) ):97-100.
Reichert T, DeBruyere M, Deneys V, et al.  Lymphocyte subset reference ranges in adult caucasians. Clin Immunol Immunopathol . 1991;;60:190-208.
Saksella E, Timonen T, Ranki A, Hayry P.  Morphological and functional characterization of isolated effector cells responsible for human natural killer activity to fetal fibroblasts and to cultured cell line targets. Immunol Rev . 1979;;44:77-123
Rabatić S, Sabioncello A, Dekaris D, Kardum I.  Age-related changes in functions of peripheral blood phagocytes. Mech Ageing Dev . 1988;;45:223-229.
Gearing AHJ, Bird CR.  Production and assay of interleukin 2.  In: Clemens MJ, Morris AG, Gearing AHJ, eds. Lymphokines and Interferons: A Practical Approach . Oxford, England: IRL Press; 1987;:291-301.
Matthews N, Neale ML.  Cytotoxicity assays for tumor necrosis factor and lymphotoxin.  In: Clemens MJ, Morris AG, Gearing AHJ, eds. Lymphokines and Interferons: A Practical Approach . Oxford, England: IRL Press; 1987;:221-225.
Denizot F, Lang R.  Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods . 1986;; 89:271-277.
Hansen MB, Ross C, Berg K.  A sensitive antiviral neutralization bioassay for measuring antibodies to interferons. J Immunol Methods . 1990;; 127:241-248.
Theodorsson-Norheim E.  Kruskal-Wallis test: BASIC computer program to perform nonparametric one-way analysis of variance and multiple comparisons on ranks of several independent samples. Comput Method Program Biomed . 1986;;23:57-62.
Homo-Delarche F, Fitzpatrick F, Christeff EA, Nunez, EA, Bach JF, Dardenne M.  Sex steroids, glucocorticoids, stress and autoimmunity. J Steroid Biochem Mol Biol . 1991;;40:616-637.
Pollock RE, Lotzova E, Stanford SD.  Mechanism of surgical stress impairment of human peri-operative natural killer cell cytotoxicity. Arch Surg . 1991;;126:338-342.
Aoki R, Usuda T, Miyakoshi H, Tamura K, Herberman R.  Low NK syndrome (LNKS): clinical and immunological features. Nat Immun Cell Growth Regul . 1987;;6:116-128.
Levy SM, Herbermen RB, Lee J, et al.  Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity. Nat Immun Cell Grow Regul . 1991;;10:289-307.
Yang KD, Hill HR.  Neutrophil function disorders: pathophysiology, prevention, and therapy. J Pediatr . 1991;;119:343-354.
Cerami A.  Inflammatory cytokines. Clin Immunol Immunopathol . 1992;;62( (suppl) ):S3-S10.
Waage A, Aasen AO.  Different role of cytokine mediators in septic shock related to meningococcal disease and surgery/polytrauma. Immunol Rev . 1992;;127:221-230.
Weigent DA, Blalock JE.  Interactions between the neuroendocrine and immune systems: common hormones and receptors. Immunol Rev . 1987;;100: 79-108.
Harbuz MS, Lightman SL.  Stress and the hypothalamo-pituitary-adrenal axis: acute, chronic and immunological activation. J Endocrinol . 1992;;134: 327-339.
Xie QW.  Experimental studies on changes of neuroendocrine functions during starvation and refeeding. Neuroendocrinology . 1991;;53( (suppl 1) ):52-59.
Ausman LM, Gallina DL, Hegsted DM.  Proteincalorie malnutrition in squirrel monkeys: adaptive response to calorie deficiency. Am J Clin Nutr . 1989;;50;19-29.
Malozowski S, Muzzo S, Vurrows R, et al.  The hypothalamic-pituitary-adrenal axis in infantile malnutrition. Clin Endocrinol . 1990;;32:461-465.
Dekaris D, Sabioncello A, Kocijan-Hercigonja D, et al.  Flow cytometric characterization of lymphocyte population in peripheral blood of Croatian war refugees. Wien Med Wochenschr . In press.
Dekaris D, Sabioncello A, Kocijan-Hercigonja D, et al. The impact of chronic psychological, environmental, and physiologic stress on immunological status of Croatian war refugees . Meeting of the European Group for Immunodeficiencies, Final program; Lugano, Switzerland. 1992;:110.
Peterson PK, Chao CC, Molitor T, Murtaugh M, Strgar F, Sharp BM.  Stress and pathogenesis of infectious disease. Rev Infect Dis . 1991;;13:710-720.

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Chrousos GP, Gold PW.  The concepts of stress and stress system disorders. JAMA . 1992;;267:1244-1252.
Khansari DN, Murgo AJ, Faith RE.  Effects of stress on the immune system. Immunol Today . 1990;;11:170-175.
O'Leary A.  Stress, emotion, and human immune function. Psychol Bull . 1990;;108:363-382.
Serban G.  Stress in affective disorders. Methods Achiev Exp Pathol . 1991;;15:200-220.
Kiecolt-Glaser JK, Glaser R.  Stress and immune function in humans.  In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology . Orlando, Fla: Academic Press Inc; 1991;:849-867.
Ballieux RE.  Impact of mental stress on the immune response. J Clin Periodontol . 1991;;18:427-430.
Bentdal ØH, Frøland SS, Djøseland O.  Alterations in serum cortisol, CD4+/CD8+ lymphocyte sub-population ration and T cell mediated suppression of immune responses in the malnutrition of anorexia nervosa. Clin Nutr . 1991;;10;167-172.
Chandra RK.  1990 McCollun Award Lecture: nutrition and immunity: lessons from the past and new insights into the future. Am J Clin Nutr . 1991;; 53:1087-1101.
Chandra RK.  Protein-energy malnutrition and immunological responses. J Nutr . 1992;;122:597-600.
Law DK, Dudrick SJ, Abdou NI.  Immunocompetence of patients with protein-calorie. Ann Intern Med . 1973;;79:545-550.
Redmond HP, Shou J, Kelly CJ, et al.  Immunosuppressive mechanisms in protein-calorie malnutrition. Surgery . 1991;;110:311-317.
Mazowiecki T.  Report of special rapporteur of the Commission on Human Rights on the situation of human rights in the territory of former Yugoslavia.  In: Report to the General Assembly of the UN . New York, NY: United Nations; 1992;:18-19. 47th General Assembly Session, agenda item 98c.
Novotny Z.  Manjača: how the Yugoslav Federal Army treats the prisoners. Croatian Med J . 1992;;(war (suppl 2) ):90-92.
Borc̆ić D, Kuzman I, Bobinac E, Beus I, Schoen wald S.  Medical status of prisoners of war from Manjača and Glina camp. Croatian Med J . 1992;; (war (suppl 2) ):93-96.
DeZan D, Anić N, Klein E.  Psychic status of the Manjača camp prisoners. Croatian Med J . 1992;; (war (suppl 2) ):97-100.
Reichert T, DeBruyere M, Deneys V, et al.  Lymphocyte subset reference ranges in adult caucasians. Clin Immunol Immunopathol . 1991;;60:190-208.
Saksella E, Timonen T, Ranki A, Hayry P.  Morphological and functional characterization of isolated effector cells responsible for human natural killer activity to fetal fibroblasts and to cultured cell line targets. Immunol Rev . 1979;;44:77-123
Rabatić S, Sabioncello A, Dekaris D, Kardum I.  Age-related changes in functions of peripheral blood phagocytes. Mech Ageing Dev . 1988;;45:223-229.
Gearing AHJ, Bird CR.  Production and assay of interleukin 2.  In: Clemens MJ, Morris AG, Gearing AHJ, eds. Lymphokines and Interferons: A Practical Approach . Oxford, England: IRL Press; 1987;:291-301.
Matthews N, Neale ML.  Cytotoxicity assays for tumor necrosis factor and lymphotoxin.  In: Clemens MJ, Morris AG, Gearing AHJ, eds. Lymphokines and Interferons: A Practical Approach . Oxford, England: IRL Press; 1987;:221-225.
Denizot F, Lang R.  Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods . 1986;; 89:271-277.
Hansen MB, Ross C, Berg K.  A sensitive antiviral neutralization bioassay for measuring antibodies to interferons. J Immunol Methods . 1990;; 127:241-248.
Theodorsson-Norheim E.  Kruskal-Wallis test: BASIC computer program to perform nonparametric one-way analysis of variance and multiple comparisons on ranks of several independent samples. Comput Method Program Biomed . 1986;;23:57-62.
Homo-Delarche F, Fitzpatrick F, Christeff EA, Nunez, EA, Bach JF, Dardenne M.  Sex steroids, glucocorticoids, stress and autoimmunity. J Steroid Biochem Mol Biol . 1991;;40:616-637.
Pollock RE, Lotzova E, Stanford SD.  Mechanism of surgical stress impairment of human peri-operative natural killer cell cytotoxicity. Arch Surg . 1991;;126:338-342.
Aoki R, Usuda T, Miyakoshi H, Tamura K, Herberman R.  Low NK syndrome (LNKS): clinical and immunological features. Nat Immun Cell Growth Regul . 1987;;6:116-128.
Levy SM, Herbermen RB, Lee J, et al.  Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity. Nat Immun Cell Grow Regul . 1991;;10:289-307.
Yang KD, Hill HR.  Neutrophil function disorders: pathophysiology, prevention, and therapy. J Pediatr . 1991;;119:343-354.
Cerami A.  Inflammatory cytokines. Clin Immunol Immunopathol . 1992;;62( (suppl) ):S3-S10.
Waage A, Aasen AO.  Different role of cytokine mediators in septic shock related to meningococcal disease and surgery/polytrauma. Immunol Rev . 1992;;127:221-230.
Weigent DA, Blalock JE.  Interactions between the neuroendocrine and immune systems: common hormones and receptors. Immunol Rev . 1987;;100: 79-108.
Harbuz MS, Lightman SL.  Stress and the hypothalamo-pituitary-adrenal axis: acute, chronic and immunological activation. J Endocrinol . 1992;;134: 327-339.
Xie QW.  Experimental studies on changes of neuroendocrine functions during starvation and refeeding. Neuroendocrinology . 1991;;53( (suppl 1) ):52-59.
Ausman LM, Gallina DL, Hegsted DM.  Proteincalorie malnutrition in squirrel monkeys: adaptive response to calorie deficiency. Am J Clin Nutr . 1989;;50;19-29.
Malozowski S, Muzzo S, Vurrows R, et al.  The hypothalamic-pituitary-adrenal axis in infantile malnutrition. Clin Endocrinol . 1990;;32:461-465.
Dekaris D, Sabioncello A, Kocijan-Hercigonja D, et al.  Flow cytometric characterization of lymphocyte population in peripheral blood of Croatian war refugees. Wien Med Wochenschr . In press.
Dekaris D, Sabioncello A, Kocijan-Hercigonja D, et al. The impact of chronic psychological, environmental, and physiologic stress on immunological status of Croatian war refugees . Meeting of the European Group for Immunodeficiencies, Final program; Lugano, Switzerland. 1992;:110.
Peterson PK, Chao CC, Molitor T, Murtaugh M, Strgar F, Sharp BM.  Stress and pathogenesis of infectious disease. Rev Infect Dis . 1991;;13:710-720.
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