Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Dec 19;92(26):12080–12084. doi: 10.1073/pnas.92.26.12080

Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection.

D F Darko 1, J C Miller 1, C Gallen 1, J White 1, J Koziol 1, S J Brown 1, R Hayduk 1, J H Atkinson 1, J Assmus 1, D T Munnell 1, et al.
PMCID: PMC40300  PMID: 8618848

Abstract

We tested the hypothesis that increases in tumor necrosis factor alpha (TNF-alpha) induced by human immunodeficiency virus (HIV) are associated with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infection. Nocturnal sleep disturbances and associated fatigue contribute to the disability of HIV infection. TNF-alpha causes fatigue in clinical use and promotes slow-wave sleep in animal models. With slow progress toward a vaccine and weak effects from current therapies, efforts are directed toward extending productive life of HIV-infected individuals and shortening the duration of disability in terminal illness. We describe previously unrecognized nocturnal cyclic variations in plasma levels of TNF-alpha in all subjects. In 6 of 10 subjects (1 control subject, 3 HIV-seropositive patients with CD4+ cell number > 400 cells per microliters, and 2 HIV-positive patients with CD4+ cell number < 400 cells per microliters), these fluctuations in TNF-alpha were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4+ cell number < 400 cells per microliters and 1 control subject. In 5 HIV subjects with abnormally low CD4+ cell counts ( < 400 cells per microliters), the number of days since seroconversion correlated significantly with low correlation between TNF-alpha and delta amplitude. We conclude that a previously unrecognized normal, physiological coupling exists between TNF-alpha and delta amplitude during sleep and that the lessened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.

Full text

PDF
12080

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aboulafia D., Miles S. A., Saks S. R., Mitsuyasu R. T. Intravenous recombinant tumor necrosis factor in the treatment of AIDS-related Kaposi's sarcoma. J Acquir Immune Defic Syndr. 1989;2(1):54–58. [PubMed] [Google Scholar]
  2. Arditi M., Kabat W., Yogev R. Serum tumor necrosis factor alpha, interleukin 1-beta, p24 antigen concentrations and CD4+ cells at various stages of human immunodeficiency virus 1 infection in children. Pediatr Infect Dis J. 1991 Jun;10(6):450–455. doi: 10.1097/00006454-199106000-00007. [DOI] [PubMed] [Google Scholar]
  3. Armitage R., Roffwarg H. P., Rush A. J., Calhoun J. S., Purdy D. G., Giles D. E. Digital period analysis of sleep EEG in depression. Biol Psychiatry. 1992 Jan 1;31(1):52–68. doi: 10.1016/0006-3223(92)90006-l. [DOI] [PubMed] [Google Scholar]
  4. Banks W. A., Kastin A. J. Blood to brain transport of interleukin links the immune and central nervous systems. Life Sci. 1991;48(25):PL117–PL121. doi: 10.1016/0024-3205(91)90385-o. [DOI] [PubMed] [Google Scholar]
  5. Banks W. A., Ortiz L., Plotkin S. R., Kastin A. J. Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain in the mouse by a shared saturable mechanism. J Pharmacol Exp Ther. 1991 Dec;259(3):988–996. [PubMed] [Google Scholar]
  6. Darko D. F., McCutchan J. A., Kripke D. F., Gillin J. C., Golshan S. Fatigue, sleep disturbance, disability, and indices of progression of HIV infection. Am J Psychiatry. 1992 Apr;149(4):514–520. doi: 10.1176/ajp.149.4.514. [DOI] [PubMed] [Google Scholar]
  7. Darko D. F., Mitler M. M., Henriksen S. J. Lentiviral infection, immune response peptides and sleep. Adv Neuroimmunol. 1995;5(1):57–77. doi: 10.1016/0960-5428(94)00044-o. [DOI] [PubMed] [Google Scholar]
  8. Feinberg I. Period/amplitude measures of delta show robust declines across nonrapid eye movement sleep episodes: a comment on Armitage and Roffwarg. Sleep. 1993 Dec;16(8):762–763. doi: 10.1093/sleep/16.8.762. [DOI] [PubMed] [Google Scholar]
  9. Glass J. D., Wesselingh S. L., Selnes O. A., McArthur J. C. Clinical-neuropathologic correlation in HIV-associated dementia. Neurology. 1993 Nov;43(11):2230–2237. doi: 10.1212/wnl.43.11.2230. [DOI] [PubMed] [Google Scholar]
  10. Hober D., Haque A., Wattre P., Beaucaire G., Mouton Y., Capron A. Production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) in patients with AIDS. Enhanced level of TNF-alpha is related to a higher cytotoxic activity. Clin Exp Immunol. 1989 Dec;78(3):329–333. [PMC free article] [PubMed] [Google Scholar]
  11. Jakubowski A. A., Casper E. S., Gabrilove J. L., Templeton M. A., Sherwin S. A., Oettgen H. F. Phase I trial of intramuscularly administered tumor necrosis factor in patients with advanced cancer. J Clin Oncol. 1989 Mar;7(3):298–303. doi: 10.1200/JCO.1989.7.3.298. [DOI] [PubMed] [Google Scholar]
  12. Kobayashi S., Hamamoto Y., Kobayashi N., Yamamoto N. Serum level of TNF alpha in HIV-infected individuals. AIDS. 1990 Feb;4(2):169–170. [PubMed] [Google Scholar]
  13. Krueger J. M., Dinarello C. A., Shoham S., Davenne D., Walter J., Kubillus S. Interferon alpha-2 enhances slow-wave sleep in rabbits. Int J Immunopharmacol. 1987;9(1):23–30. doi: 10.1016/0192-0561(87)90107-x. [DOI] [PubMed] [Google Scholar]
  14. Krueger J. M., Walter J., Dinarello C. A., Wolff S. M., Chedid L. Sleep-promoting effects of endogenous pyrogen (interleukin-1). Am J Physiol. 1984 Jun;246(6 Pt 2):R994–R999. doi: 10.1152/ajpregu.1984.246.6.R994. [DOI] [PubMed] [Google Scholar]
  15. Kubicki S., Henkes H., Alm D., Scheuler W., Pohle H. D., Ruf B., Könneke J. Schlafpolygraphische Daten von AIDS-Patienten. EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb. 1989 Dec;20(4):288–294. [PubMed] [Google Scholar]
  16. Kupfer D. J., Ehlers C. L., Frank E., Grochocinski V. J., McEachran A. B., Buhari A. Persistent effects of antidepressants: EEG sleep studies in depressed patients during maintenance treatment. Biol Psychiatry. 1994 May 15;35(10):781–793. doi: 10.1016/0006-3223(94)91140-1. [DOI] [PubMed] [Google Scholar]
  17. Lau A. S., Livesey J. F. Endotoxin induction of tumor necrosis factor is enhanced by acid-labile interferon-alpha in acquired immunodeficiency syndrome. J Clin Invest. 1989 Sep;84(3):738–743. doi: 10.1172/JCI114231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Maury C. P., Lăhdevirta J. Correlation of serum cytokine levels with haematological abnormalities in human immunodeficiency virus infection. J Intern Med. 1990 Apr;227(4):253–257. doi: 10.1111/j.1365-2796.1990.tb00154.x. [DOI] [PubMed] [Google Scholar]
  19. Moeller A. A., Wiegand M., Oechsner M., Krieg J. C., Holsboer F., Emminger C. Effects of zidovudine on EEG sleep in HIV-infected men. J Acquir Immune Defic Syndr. 1992;5(6):636–637. [PubMed] [Google Scholar]
  20. Norman S. E., Chediak A. D., Freeman C., Kiel M., Mendez A., Duncan R., Simoneau J., Nolan B. Sleep disturbances in men with asymptomatic human immunodeficiency (HIV) infection. Sleep. 1992 Apr;15(2):150–155. doi: 10.1093/sleep/15.2.150. [DOI] [PubMed] [Google Scholar]
  21. Norman S. E., Resnick L., Cohn M. A., Duara R., Herbst J., Berger J. R. Sleep disturbances in HIV-seropositive patients. JAMA. 1988 Aug 19;260(7):922–922. [PubMed] [Google Scholar]
  22. Odeh M. The role of tumour necrosis factor-alpha in acquired immunodeficiency syndrome. J Intern Med. 1990 Dec;228(6):549–556. doi: 10.1111/j.1365-2796.1990.tb00278.x. [DOI] [PubMed] [Google Scholar]
  23. Rautonen J., Rautonen N., Martin N. L., Philip R., Wara D. W. Serum interleukin-6 concentrations are elevated and associated with elevated tumor necrosis factor-alpha and immunoglobulin G and A concentrations in children with HIV infection. AIDS. 1991 Nov;5(11):1319–1325. doi: 10.1097/00002030-199111000-00006. [DOI] [PubMed] [Google Scholar]
  24. Reddy M. M., Sorrell S. J., Lange M., Grieco M. H. Tumor necrosis factor and HIV P24 antigen levels in serum of HIV-infected populations. J Acquir Immune Defic Syndr. 1988;1(5):436–440. [PubMed] [Google Scholar]
  25. Roux-Lombard P., Modoux C., Cruchaud A., Dayer J. M. Purified blood monocytes from HIV 1-infected patients produce high levels of TNF alpha and IL-1. Clin Immunol Immunopathol. 1989 Mar;50(3):374–384. doi: 10.1016/0090-1229(89)90144-x. [DOI] [PubMed] [Google Scholar]
  26. Shibata M., Blatteis C. M. Human recombinant tumor necrosis factor and interferon affect the activity of neurons in the organum vasculosum laminae terminalis. Brain Res. 1991 Oct 25;562(2):323–326. doi: 10.1016/0006-8993(91)90639-d. [DOI] [PubMed] [Google Scholar]
  27. Shoham S., Davenne D., Cady A. B., Dinarello C. A., Krueger J. M. Recombinant tumor necrosis factor and interleukin 1 enhance slow-wave sleep. Am J Physiol. 1987 Jul;253(1 Pt 2):R142–R149. doi: 10.1152/ajpregu.1987.253.1.R142. [DOI] [PubMed] [Google Scholar]
  28. Steinmetz T., Schaadt M., Gähl R., Schenk V., Diehl V., Pfreundschuh M. Phase I study of 24-hour continuous intravenous infusion of recombinant human tumor necrosis factor. J Biol Response Mod. 1988 Oct;7(5):417–423. [PubMed] [Google Scholar]
  29. Voth R., Rossol S., Klein K., Hess G., Schütt K. H., Schröder H. C., Meyer zum Büschenfelde K. H., Müller W. E. Differential gene expression of IFN-alpha and tumor necrosis factor-alpha in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS. J Immunol. 1990 Feb 1;144(3):970–975. [PubMed] [Google Scholar]
  30. Wesselingh S. L., Power C., Glass J. D., Tyor W. R., McArthur J. C., Farber J. M., Griffin J. W., Griffin D. E. Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. Ann Neurol. 1993 Jun;33(6):576–582. doi: 10.1002/ana.410330604. [DOI] [PubMed] [Google Scholar]
  31. White J. L., Darko D. F., Brown S. J., Miller J. C., Hayduk R., Kelly T., Mitler M. M. Early central nervous system response to HIV infection: sleep distortion and cognitive-motor decrements. AIDS. 1995 Sep;9(9):1043–1050. doi: 10.1097/00002030-199509000-00009. [DOI] [PubMed] [Google Scholar]
  32. Wiedenmann B., Reichardt P., Räth U., Theilmann L., Schüle B., Ho A. D., Schlick E., Kempeni J., Hunstein W., Kommerell B. Phase-I trial of intravenous continuous infusion of tumor necrosis factor in advanced metastatic carcinomas. J Cancer Res Clin Oncol. 1989;115(2):189–192. doi: 10.1007/BF00397922. [DOI] [PubMed] [Google Scholar]
  33. Wiegand M., Möller A. A., Schreiber W., Krieg J. C., Fuchs D., Wachter H., Holsboer F. Nocturnal sleep EEG in patients with HIV infection. Eur Arch Psychiatry Clin Neurosci. 1991;240(3):153–158. doi: 10.1007/BF02190756. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES