Abstract
Seventy-nine human immunodeficiency virus type 1 (HIV-1)-seropositive homosexual men participating in a longitudinal study of HIV-1 infection were assessed twice, 6 months apart, to investigate associations between bereavement and cellular immune function. Subjects were assessed by using a theory-driven model comprising life stressors, social support and coping style, and control variables. Natural killer cell cytotoxicity was decreased among the bereaved at both times. Lymphocyte proliferative response to phytohemagglutinin was decreased among the bereaved at the second time point but not at the first. These functional immune decrements are associated with increased neuroendocrine responses of the sympathetic adrenomeduallary system as well as the limbic-hypothalamic-pituitary-adrenal axis. Implications for differential neuroendocrine responses over time are discussed. Active coping style was independently and positively related to both immune measures. The results imply that a bereavement support group intervention merits investigation for an effect on immunological measures and clinical progression of HIV-1 infection as well as grief resolution.
Full Text
The Full Text of this article is available as a PDF (287.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahmad A., Menezes J. Positive correlation between the natural killer and gp 120/41-specific antibody-dependent cellular cytotoxic effector functions in HIV-infected individuals. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):115–119. doi: 10.1097/00042560-199510020-00002. [DOI] [PubMed] [Google Scholar]
- Baron G. C., Klimas N. G., Fischl M. A., Fletcher M. A. Decreased natural cell-mediated cytotoxicity per effector cell in acquired immunodeficiency syndrome. Diagn Immunol. 1985;3(4):197–204. [PubMed] [Google Scholar]
- Bartrop R. W., Luckhurst E., Lazarus L., Kiloh L. G., Penny R. Depressed lymphocyte function after bereavement. Lancet. 1977 Apr 16;1(8016):834–836. doi: 10.1016/s0140-6736(77)92780-5. [DOI] [PubMed] [Google Scholar]
- Baum M. K., Shor-Posner G., Lu Y., Rosner B., Sauberlich H. E., Fletcher M. A., Szapocznik J., Eisdorfer C., Buring J. E., Hennekens C. H. Micronutrients and HIV-1 disease progression. AIDS. 1995 Sep;9(9):1051–1056. doi: 10.1097/00002030-199509000-00010. [DOI] [PubMed] [Google Scholar]
- Beisel W. R., Edelman R., Nauss K., Suskind R. M. Single-nutrient effects on immunologic functions. Report of a workshop sponsored by the Department of Food and Nutrition and its nutrition advisory group of the American Medical Association. JAMA. 1981 Jan 2;245(1):53–58. doi: 10.1001/jama.245.1.53. [DOI] [PubMed] [Google Scholar]
- Bieri J. G., Tolliver T. J., Catignani G. L. Simultaneous determination of alpha-tocopherol and retinol in plasma or red cells by high pressure liquid chromatography. Am J Clin Nutr. 1979 Oct;32(10):2143–2149. doi: 10.1093/ajcn/32.10.2143. [DOI] [PubMed] [Google Scholar]
- Bodnar J. C., Kiecolt-Glaser J. K. Caregiver depression after bereavement: chronic stress isn't over when it's over. Psychol Aging. 1994 Sep;9(3):372–380. doi: 10.1037//0882-7974.9.3.372. [DOI] [PubMed] [Google Scholar]
- Burack J. H., Barrett D. C., Stall R. D., Chesney M. A., Ekstrand M. L., Coates T. J. Depressive symptoms and CD4 lymphocyte decline among HIV-infected men. JAMA. 1993 Dec 1;270(21):2568–2573. [PubMed] [Google Scholar]
- Carver C. S., Scheier M. F., Weintraub J. K. Assessing coping strategies: a theoretically based approach. J Pers Soc Psychol. 1989 Feb;56(2):267–283. doi: 10.1037//0022-3514.56.2.267. [DOI] [PubMed] [Google Scholar]
- Claman H. N. Corticosteroids and lymphoid cells. N Engl J Med. 1972 Aug 24;287(8):388–397. doi: 10.1056/NEJM197208242870806. [DOI] [PubMed] [Google Scholar]
- Clerici M., Bevilacqua M., Vago T., Villa M. L., Shearer G. M., Norbiato G. An immunoendocrinological hypothesis of HIV infection. Lancet. 1994 Jun 18;343(8912):1552–1553. doi: 10.1016/s0140-6736(94)92944-0. [DOI] [PubMed] [Google Scholar]
- Dhabhar F. S., Miller A. H., McEwen B. S., Spencer R. L. Effects of stress on immune cell distribution. Dynamics and hormonal mechanisms. J Immunol. 1995 May 15;154(10):5511–5527. [PubMed] [Google Scholar]
- Evans D. L., Leserman J., Perkins D. O., Stern R. A., Murphy C., Tamul K., Liao D., van der Horst C. M., Hall C. D., Folds J. D. Stress-associated reductions of cytotoxic T lymphocytes and natural killer cells in asymptomatic HIV infection. Am J Psychiatry. 1995 Apr;152(4):543–550. doi: 10.1176/ajp.152.4.543. [DOI] [PubMed] [Google Scholar]
- Fletcher M. A., Baron G. C., Ashman M. R., Fischl M. A., Klimas N. G. Use of whole blood methods in assessment of immune parameters in immunodeficiency states. Diagn Clin Immunol. 1987;5(2):69–81. [PubMed] [Google Scholar]
- Folkman S., Chesney M. A., Cooke M., Boccellari A., Collette L. Caregiver burden in HIV-positive and HIV-negative partners of men with AIDS. J Consult Clin Psychol. 1994 Aug;62(4):746–756. doi: 10.1037//0022-006x.62.4.746. [DOI] [PubMed] [Google Scholar]
- Goodkin K., Blaney N. T., Feaster D., Fletcher M. A., Baum M. K., Mantero-Atienza E., Klimas N. G., Millon C., Szapocznik J., Eisdorfer C. Active coping style is associated with natural killer cell cytotoxicity in asymptomatic HIV-1 seropositive homosexual men. J Psychosom Res. 1992 Oct;36(7):635–650. doi: 10.1016/0022-3999(92)90053-5. [DOI] [PubMed] [Google Scholar]
- Goodkin K., Fletcher M. A., Cohen N. Clinical aspects of psychoneuroimmunology. Lancet. 1995 Jan 21;345(8943):183–184. doi: 10.1016/s0140-6736(95)90180-9. [DOI] [PubMed] [Google Scholar]
- Goodkin K., Fuchs I., Feaster D., Leeka J., Rishel D. D. Life stressors and coping style are associated with immune measures in HIV-1 infection--a preliminary report. Int J Psychiatry Med. 1992;22(2):155–172. doi: 10.2190/BD46-F4JD-K8TW-RUFH. [DOI] [PubMed] [Google Scholar]
- Goodkin K., Mulder C. L., Blaney N. T., Ironson G., Kumar M., Fletcher M. A. Psychoneuroimmunology and human immunodeficiency virus type 1 infection revisited. Arch Gen Psychiatry. 1994 Mar;51(3):246–248. doi: 10.1001/archpsyc.1994.03950030082007. [DOI] [PubMed] [Google Scholar]
- Ingenbleek Y., Van Den Schrieck H. G., De Nayer P., De Visscher M. Albumin, transferrin and the thyroxine-binding prealbumin/retinol-binding protein (TBPA-RBP) complex in assessment of malnutrition. Clin Chim Acta. 1975 Aug 18;63(1):61–67. doi: 10.1016/0009-8981(75)90379-4. [DOI] [PubMed] [Google Scholar]
- Ironson G., Friedman A., Klimas N., Antoni M., Fletcher M. A., Laperriere A., Simoneau J., Schneiderman N. Distress, denial, and low adherence to behavioral interventions predict faster disease progression in gay men infected with human immunodeficiency virus. Int J Behav Med. 1994;1(1):90–105. doi: 10.1207/s15327558ijbm0101_6. [DOI] [PubMed] [Google Scholar]
- Irwin M., Daniels M., Risch S. C., Bloom E., Weiner H. Plasma cortisol and natural killer cell activity during bereavement. Biol Psychiatry. 1988 Jun;24(2):173–178. doi: 10.1016/0006-3223(88)90272-7. [DOI] [PubMed] [Google Scholar]
- Irwin M., Daniels M., Smith T. L., Bloom E., Weiner H. Impaired natural killer cell activity during bereavement. Brain Behav Immun. 1987 Mar;1(1):98–104. doi: 10.1016/0889-1591(87)90011-0. [DOI] [PubMed] [Google Scholar]
- Jacobs S., Kasl S., Schaefer C., Ostfeld A. Conscious and unconscious coping with loss. Psychosom Med. 1994 Nov-Dec;56(6):557–563. doi: 10.1097/00006842-199411000-00012. [DOI] [PubMed] [Google Scholar]
- Kemeny M. E., Weiner H., Taylor S. E., Schneider S., Visscher B., Fahey J. L. Repeated bereavement, depressed mood, and immune parameters in HIV seropositive and seronegative gay men. Health Psychol. 1994 Jan;13(1):14–24. doi: 10.1037//0278-6133.13.1.14. [DOI] [PubMed] [Google Scholar]
- Kessler R. C., Foster C., Joseph J., Ostrow D., Wortman C., Phair J., Chmiel J. Stressful life events and symptom onset in HIV infection. Am J Psychiatry. 1991 Jun;148(6):733–738. doi: 10.1176/ajp.148.6.733. [DOI] [PubMed] [Google Scholar]
- Kiecolt-Glaser J. K., Glaser R. Methodological issues in behavioral immunology research with humans. Brain Behav Immun. 1988 Mar;2(1):67–78. doi: 10.1016/0889-1591(88)90007-4. [DOI] [PubMed] [Google Scholar]
- Klimas N. G., Caralis P., LaPerriere A., Antoni M. H., Ironson G., Simoneau J., Schneiderman N., Fletcher M. A. Immunologic function in a cohort of human immunodeficiency virus type 1-seropositive and -negative healthy homosexual men. J Clin Microbiol. 1991 Jul;29(7):1413–1421. doi: 10.1128/jcm.29.7.1413-1421.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kumar M., Kumar A. M., Morgan R., Szapocznik J., Eisdorfer C. Abnormal pituitary-adrenocortical response in early HIV-1 infection. J Acquir Immune Defic Syndr. 1993 Jan;6(1):61–65. [PubMed] [Google Scholar]
- Kumar M., Morgan R., Szapocznik J., Eisdorfer C. Norepinephrine response in early HIV infection. J Acquir Immune Defic Syndr. 1991;4(8):782–786. [PubMed] [Google Scholar]
- LAU K. S., GOTTLIEB C., WASSERMAN L. R., HERBERT V. MEASUREMENT OF SERUM VITAMIN B12 LEVEL USING RADIOISOTOPE DILUTION AND COATED CHARCOAL. Blood. 1965 Aug;26:202–214. [PubMed] [Google Scholar]
- Lee W., Hamernyik P., Hutchinson M., Raisys V. A., Labbé R. F. Ascorbic acid in lymphocytes: cell preparation and liquid-chromatographic assay. Clin Chem. 1982 Oct;28(10):2165–2169. [PubMed] [Google Scholar]
- Linn M. W., Linn B. S., Jensen J. Stressful events, dysphoric mood, and immune responsiveness. Psychol Rep. 1984 Feb;54(1):219–222. doi: 10.2466/pr0.1984.54.1.219. [DOI] [PubMed] [Google Scholar]
- Lyketsos C. G., Hoover D. R., Guccione M., Senterfitt W., Dew M. A., Wesch J., VanRaden M. J., Treisman G. J., Morgenstern H. Depressive symptoms as predictors of medical outcomes in HIV infection. Multicenter AIDS Cohort Study. JAMA. 1993 Dec 1;270(21):2563–2567. [PubMed] [Google Scholar]
- Martin J. L., Dean L. Effects of AIDS-related bereavement and HIV-related illness on psychological distress among gay men: a 7-year longitudinal study, 1985-1991. J Consult Clin Psychol. 1993 Feb;61(1):94–103. doi: 10.1037//0022-006x.61.1.94. [DOI] [PubMed] [Google Scholar]
- Martin J. L. Psychological consequences of AIDS-related bereavement among gay men. J Consult Clin Psychol. 1988 Dec;56(6):856–862. doi: 10.1037//0022-006x.56.6.856. [DOI] [PubMed] [Google Scholar]
- Meyaard L., Otto S. A., Keet I. P., van Lier R. A., Miedema F. Changes in cytokine secretion patterns of CD4+ T-cell clones in human immunodeficiency virus infection. Blood. 1994 Dec 15;84(12):4262–4268. [PubMed] [Google Scholar]
- Milne D. B., Ralston N. V., Wallwork J. C. Zinc content of cellular components of blood: methods for cell separation and analysis evaluated. Clin Chem. 1985 Jan;31(1):65–69. [PubMed] [Google Scholar]
- Nair M. P., Schwartz S. A. Synergistic effect of cortisol and HIV-1 envelope peptide on the NK activities of normal lymphocytes. Brain Behav Immun. 1995 Mar;9(1):20–30. doi: 10.1006/brbi.1995.1003. [DOI] [PubMed] [Google Scholar]
- Neugebauer R., Rabkin J. G., Williams J. B., Remien R. H., Goetz R., Gorman J. M. Bereavement reactions among homosexual men experiencing multiple losses in the AIDS epidemic. Am J Psychiatry. 1992 Oct;149(10):1374–1379. doi: 10.1176/ajp.149.10.1374. [DOI] [PubMed] [Google Scholar]
- Parkes C. M., Brown R. J. Health after bereavement. A controlled study of young Boston widows and widowers. Psychosom Med. 1972 Sep-Oct;34(5):449–461. doi: 10.1097/00006842-197209000-00008. [DOI] [PubMed] [Google Scholar]
- Perry S., Fishman B., Jacobsberg L., Frances A. Relationships over 1 year between lymphocyte subsets and psychosocial variables among adults with infection by human immunodeficiency virus. Arch Gen Psychiatry. 1992 May;49(5):396–401. doi: 10.1001/archpsyc.1992.01820050060010. [DOI] [PubMed] [Google Scholar]
- Prigerson H. G., Frank E., Kasl S. V., Reynolds C. F., 3rd, Anderson B., Zubenko G. S., Houck P. R., George C. J., Kupfer D. J. Complicated grief and bereavement-related depression as distinct disorders: preliminary empirical validation in elderly bereaved spouses. Am J Psychiatry. 1995 Jan;152(1):22–30. doi: 10.1176/ajp.152.1.22. [DOI] [PubMed] [Google Scholar]
- Rabkin J. G., Williams J. B., Remien R. H., Goetz R., Kertzner R., Gorman J. M. Depression, distress, lymphocyte subsets, and human immunodeficiency virus symptoms on two occasions in HIV-positive homosexual men. Arch Gen Psychiatry. 1991 Feb;48(2):111–119. doi: 10.1001/archpsyc.1991.01810260019002. [DOI] [PubMed] [Google Scholar]
- Reed G. M., Kemeny M. E., Taylor S. E., Wang H. Y., Visscher B. R. Realistic acceptance as a predictor of decreased survival time in gay men with AIDS. Health Psychol. 1994 Jul;13(4):299–307. doi: 10.1037//0278-6133.13.4.299. [DOI] [PubMed] [Google Scholar]
- Rees W. D., Lutkins S. G. Mortality of bereavement. Br Med J. 1967 Oct 7;4(5570):13–16. doi: 10.1136/bmj.4.5570.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sahs J. A., Goetz R., Reddy M., Rabkin J. G., Williams J. B., Kertzner R., Gorman J. M. Psychological distress and natural killer cells in gay men with and without HIV infection. Am J Psychiatry. 1994 Oct;151(10):1479–1484. doi: 10.1176/ajp.151.10.1479. [DOI] [PubMed] [Google Scholar]
- Sarason I. G., Johnson J. H., Siegel J. M. Assessing the impact of life changes: development of the Life Experiences Survey. J Consult Clin Psychol. 1978 Oct;46(5):932–946. doi: 10.1037//0022-006x.46.5.932. [DOI] [PubMed] [Google Scholar]
- Schleifer S. J., Keller S. E., Camerino M., Thornton J. C., Stein M. Suppression of lymphocyte stimulation following bereavement. JAMA. 1983 Jul 15;250(3):374–377. [PubMed] [Google Scholar]
- Scott J. M., Ghanta V., Herbert V. Trouble-free microbiologic serum and red cell folate assays. Am J Med Technol. 1974 Mar;40(3):125–134. [PubMed] [Google Scholar]
- Spurrell M. T., Creed F. H. Lymphocyte response in depressed patients and subjects anticipating bereavement. Br J Psychiatry. 1993 Jan;162:60–64. doi: 10.1192/bjp.162.1.60. [DOI] [PubMed] [Google Scholar]
- Stein M., Miller A. H., Trestman R. L. Depression, the immune system, and health and illness. Findings in search of meaning. Arch Gen Psychiatry. 1991 Feb;48(2):171–177. doi: 10.1001/archpsyc.1991.01810260079012. [DOI] [PubMed] [Google Scholar]
- Warzynski M. J., Barbour S. D., Winkler-Pickett R. T., Ortaldo J. R. CD3+, CD56+ non-MHC restricted cytotoxic T lymphocytes in two fraternal AIDS patients: a case report. Cytometry. 1994 Dec 15;18(4):231–236. doi: 10.1002/cyto.990180408. [DOI] [PubMed] [Google Scholar]
- Wilkie F. L., Eisdorfer C., Morgan R., Loewenstein D. A., Szapocznik J. Cognition in early human immunodeficiency virus infection. Arch Neurol. 1990 Apr;47(4):433–440. doi: 10.1001/archneur.1990.00530040085022. [DOI] [PubMed] [Google Scholar]
- Willett W. C., Sampson L., Stampfer M. J., Rosner B., Bain C., Witschi J., Hennekens C. H., Speizer F. E. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol. 1985 Jul;122(1):51–65. doi: 10.1093/oxfordjournals.aje.a114086. [DOI] [PubMed] [Google Scholar]
- Wortman C. B., Silver R. C. The myths of coping with loss. J Consult Clin Psychol. 1989 Jun;57(3):349–357. doi: 10.1037//0022-006x.57.3.349. [DOI] [PubMed] [Google Scholar]
- Yalom I. D., Vinogradov S. Bereavement groups: techniques and themes. Int J Group Psychother. 1988 Oct;38(4):419–457. doi: 10.1080/00207284.1988.11491130. [DOI] [PubMed] [Google Scholar]
- Zisook S., Shuchter S. R., Irwin M., Darko D. F., Sledge P., Resovsky K. Bereavement, depression, and immune function. Psychiatry Res. 1994 Apr;52(1):1–10. doi: 10.1016/0165-1781(94)90114-7. [DOI] [PubMed] [Google Scholar]