Skip to main content
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1988 Apr;26(2):176–179. doi: 10.1007/BF00205612

Effects of phenytoin on cell-mediated immunity

Yutaka Okamoto 1,, Keiji Shimizu 1, Kazuyoshi Tamura 1, Yasuyoshi Miyao 1, Masanobu Yamada 1, Nobuyuki Tsuda 1, Yutaka Matsui 1, Heitaro Mogami 1
PMCID: PMC11038969  PMID: 3258793

Abstract

The effects of phenytoin on cellular immunity were examined in murine models. Fresh splenocytes were obtained from mice which had received 1 mg/day of phenytoin i.p. for 28 days. The serum concentration of phenytoin in these animals was 10–10 μg/ml. The proliferative response of splenocytes to mitogens was assessed by 3H-thymidine incorporation. The cytotoxic activities of cells such as natural killer (NK) cells, cytotoxic T lymphocytes (CTL), and lymphokine-activated killer (LAK) cells were estimated by a 4-h 51Cr release assay. The 3H-thymidine incorporation of splenocytes was reduced significantly (P<0.01) in phenytoin-treated mice. The NK and CTL activities of splenocytes from phenytoin-treated mice were significantly suppressed. However, the LAK activity of phenytoin-treated mice was equal to that of control mice.

Keywords: Cancer Research, Natural Killer, Serum Concentration, Control Mouse, Cytotoxic Activity

References

  • 1.Alter BBJ, Grillot-Courvalin C, Bach ML, Zier KS, Sondel PM, Bach FH. Secondary cell-mediated lympholysis: Importance of H-2 LD and SD factors. J Exp Med. 1976;143:1005. doi: 10.1084/jem.143.5.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Bardana EJ, Gabourel JD, Davis GH, Craig S. Effects of phenytoin on man's immunity. Am J Med. 1983;74:289. doi: 10.1016/0002-9343(83)90630-7. [DOI] [PubMed] [Google Scholar]
  • 3.Barker CF, Billingham RE. Immunologically privileged site. Adv Immunol. 1977;25:11. [PubMed] [Google Scholar]
  • 4.Bluming A, Homer S, Khiroya R. Selective diphenylhydantoin-induced suppression of lymphocytes reacting in vitro. J Lab Clin Med. 1976;88:417. [PubMed] [Google Scholar]
  • 5.Booker HE, Darcey BA. Enzymatic immunoassay vs. gas/liquid chromatography for determination of phenobarbital and diphenylhydantoin in serum. Clin Chem. 1975;21:1766. [PubMed] [Google Scholar]
  • 6.Carrel S, de Tribolet N, Gross N. Expression of HLADR and common acute lymphoblastic leukemia antigens on glioma cells. Eur J Immunol. 1982;12:354. doi: 10.1002/eji.1830120418. [DOI] [PubMed] [Google Scholar]
  • 7.Dorsch HM, Jason J, Gelfand EW. Transient antibody deficiency and abnormal T-suppressor cells induced by phenytoin. N Engl J Med. 1982;306:406. doi: 10.1056/NEJM198202183060707. [DOI] [PubMed] [Google Scholar]
  • 8.Gagourel JD, Davis GH, Bardana EJ, Ratzlaff NA. Phenytoin influence on human lymphocyte mitogen response. Epilepsia. 1982;23:367. doi: 10.1111/j.1528-1157.1982.tb05422.x. [DOI] [PubMed] [Google Scholar]
  • 9.Grob PJ, Herold GE. Immunological abnormalities and hydantoins. Br Med J. 1972;2:561. doi: 10.1136/bmj.2.5813.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Kikuchi K, McCormic CI, Neuwelt EA. Immunosupression by phenytoin: implicant for altered immune competance in brain-tumor patients. J Neurosurg. 1984;61:1085. doi: 10.3171/jns.1984.61.6.1085. [DOI] [PubMed] [Google Scholar]
  • 11.Mackinney AA, Vyas R, Powers K. Morphologic effect of hydantoin drugs on mitosis and microtubles of cultured human lymphocytes. J Pharmacol Exp Ther. 1978;204:195. [PubMed] [Google Scholar]
  • 12.Nagai M, Arai T. Clinical effect of interferon in malignant brain tumors. Neurosurg Rev. 1984;7:55. doi: 10.1007/BF01743290. [DOI] [PubMed] [Google Scholar]
  • 13.Neuwelt EA, Kikuchi K, Hill S, Lipsky P. Immune response in patients with brain tumors. Cancer. 1983;51:248. doi: 10.1002/1097-0142(19830115)51:2<248::aid-cncr2820510214>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  • 14.Okamoto Y, Shimizu K, Miyao Y, Ushio Y, Matsui Y, Hayakawa T, Tsuda N, Mogami H. The in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) cells induced by recombinant IL-2. Brain and Nerve. 1986;38:233. [PubMed] [Google Scholar]
  • 15.Okamoto Y, Shimizu K, Miyao Y, Yamada M, Ushio Y, Matsui Y, Hayakawa T, Tago H, Ikeda H. Clinical studies of adoptive immunotherapy of human disseminated brain tumors with LAK cells and recombinant interleukin-2. Brain and Nerve. 1986;38:593. [PubMed] [Google Scholar]
  • 16.Raju S, Grogan JB. Immunologic study of the brain as a previleged site. Transplant Proc. 1977;9:1187. [PubMed] [Google Scholar]
  • 17.Roszman L, Brooks H. Immunobiology of primary intracranial tumors. Clin Exp Immunol. 1980;39:395. [PMC free article] [PubMed] [Google Scholar]
  • 18.Shimizu K, Miyao Y, Okamoto Y, Matsui Y, Ushio Y, Tsuda N, Hayakawa T, Ishida N, Mogami H. The anti-tumor efficacy of lymphokine-activated killer (LAK) cells induced in vitro from peripheral blood lymphocytes of patients with malignant glioma. Brain and Nerve. 1986;38:265. [PubMed] [Google Scholar]
  • 19.Shimizu K, Yutaka O, Miyao Y, Yamada Y, Ushio Y, Hayakawa T, Ikeda H, Mogami H. Adoptive immunotherapy of human meningeal gliomatosis and carcinomatosis with LAK cells and recombinant interleukin-2. J Neurosurg. 1987;66:519. doi: 10.3171/jns.1987.66.4.0519. [DOI] [PubMed] [Google Scholar]
  • 20.Sorrel TC, Forbes IJ. Depression of immune competance by phenytoin and carbamazepine. Clin Exp Immunol. 1975;20:273. [PMC free article] [PubMed] [Google Scholar]
  • 21.Ting JP, Nixon DF, Weiner LP, Frelinger JA. Brain Ia antigens have a bone marrow origin. Immunogenetics. 1983;17:295. doi: 10.1007/BF00364413. [DOI] [PubMed] [Google Scholar]
  • 22.Wangel AG, Arrilommi, Jokinen I. The effect of phenytoin in vitro on normal human mononuclear cells of different Ig isotype specificities. Immunobiology. 1985;170:232. doi: 10.1016/S0171-2985(85)80094-2. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES