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Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 2013 Jul 9;17(2):130–134. doi: 10.1007/BF00200049

Depression of murine natural killer cell cytotoxicity by isobutyl nitrite

Eva Lotzová 1,, Cherylyn A Savary 1, Evan M Hersh 1, Abbas A Khan 1, Michael Rosenblum 1
PMCID: PMC11039121  PMID: 6235910

Abstract

We have investigated the effect of isobutyl nitrite on murine NK-cell antitumor-directed cytotoxicity. This agent has been suggested as one of the factors underlying immunodeficiency syndrome (AIDS) in man. We demonstrated that two injections, each of 0.25 ml isobutyl nitrite, resulted in significant depression of endogenous splenic and peripheral blood natural killer (NK) cell cytotoxicity against T-cell lymphoma, YAC-1. In addition to endogenous NK cells, activity of pyrimidinol-activated NK cells was also substantially depressed by this agent. The latter observation is of the utmost importance, since it suggests that the attempt to augment NK-cell activity (to promote resistance to infections and malignancies) could fail in patients with AIDS who are isobutyl nitrite users. Isobutyl nitrite was NK-cell-suppressive not only after in vivo administration but, most importantly, also after inhalation. This indicates that isobutyl nitrite, via its NK-cell suppressive effect, could contribute to immunodeficiency in AIDS. Studies on the mechanism of NK-cell depression by isobutyl nitrite demonstrated that the NK-cell tumor-binding properties as well as NK-cell cytotoxic potential were substantially depressed. Mixing experiments failed to reveal any regulation by suppressor cell activities. The results of these studies clearly indicate that isobutyl nitrite is an immunosuppressive agent and that its use should be avoided.

Keywords: Activate Natural Killer Cell, B6D2F1 Mouse, Nylon Wool, Lytic Unit, Isobutyl Nitrite

Footnotes

Abbreviations used: NK, natural killer; S-RPMI 1640, supplemented tissue culture medium 1640; HEPES, N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid; TBC, tumor-binding cells; C-TBC, cytotoxic tumor-binding cells; AIPP, 2-amino-5-iodo-6-phenyl-4 pyrimidinol; LU, lytic units; T:E, target-to-effector; AIDS, acquired immunodeficiency syndrome

References

  • 1.Beaumont TJ, Roder JC, Elliott BE, et al. A comparative analysis of cell surface markers on murine NK cells and CTL target-effector conjugates. Scand J Immunol. 1982;16:123. doi: 10.1111/j.1365-3083.1982.tb00706.x. [DOI] [PubMed] [Google Scholar]
  • 2.Durack DT. Opportunistic infections and Kaposi's sarcoma in homosexual men. N Engl J Med. 1981;305:1465. doi: 10.1056/NEJM198112103052408. [DOI] [PubMed] [Google Scholar]
  • 3.Goedert JJ, Neuland CY, Wallen WC, et al. Amyl nitrite may alter T lymphocytes in homosexual men. Lancet. 1982;1:412. doi: 10.1016/S0140-6736(82)91617-8. [DOI] [PubMed] [Google Scholar]
  • 4.Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystic carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: Evidence of a new acquired cellular immunodeficiency. N Eng J Med. 1981;305:1425. doi: 10.1056/NEJM198112103052401. [DOI] [PubMed] [Google Scholar]
  • 5.Grimm E, Bonavida B. Mechanism of cell-mediated cytotoxicity at the single cell level. I. Estimation of cytotoxic T lymphocyte frequency and relative lytic efficiency. J Immunol. 1979;123:2861. [PubMed] [Google Scholar]
  • 6.Haley JT. Review of the physiological effects of amyl, butyl and isobutyl nitrites. Clin Toxicol. 1980;16:317. doi: 10.3109/15563658008989955. [DOI] [PubMed] [Google Scholar]
  • 7.Hanna N, Fidler IJ. Role of natural killer cells in the destruction of circulating tumor emboli. J Natl Cancer Inst. 1980;65:801. doi: 10.1093/jnci/65.4.801. [DOI] [PubMed] [Google Scholar]
  • 8.Herberman RB, Ortaldo JR. Natural killer cells. Their role in defenses against disease. Science. 1981;214:24. doi: 10.1126/science.7025208. [DOI] [PubMed] [Google Scholar]
  • 9.Hersh EM, Reuben JM, Bogerd H, et al. Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production. Cancer Res. 1983;43:1365. [PubMed] [Google Scholar]
  • 10.Hymes KB, Cheung T, Green JB, et al. Kaposi's sarcoma in homosexual men — a report of eight cases. Lancet. 1981;2:598. doi: 10.1016/S0140-6736(81)92740-9. [DOI] [PubMed] [Google Scholar]
  • 11.Julius MH, Simpson E, Herzenberg LA. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973;3:645. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  • 12.Lotzová E. Induction of unresponsiveness to bone marrow grafts. J Immunol. 1977;119:543. [PubMed] [Google Scholar]
  • 13.Lotzová E. Function of natural killer cells in various biological phenomena. Surv Synth Pathol Res. 1983;2:41. [Google Scholar]
  • 14.Lotzová E, McCredie KB. Natural killer cells in mice and man and their possible biological significance. Cancer Immunol Immunother. 1978;4:215. doi: 10.1007/BF00200151. [DOI] [Google Scholar]
  • 15.Lotzová E, Savary CA. Parallelism between the effect of cortisone acetate on hybrid resistance and natural killing. Exp Hematol. 1981;9:766. [PubMed] [Google Scholar]
  • 16.Lotzová E, Savary CA, Stringfellow DA. 5-Halo-6-phenyl pyrimidinones. New molecules with cancer therapeutic potential and interferon-inducing capacity are strong inducers of murine natural killer cells. J Immunol. 1983;130:965. [PubMed] [Google Scholar]
  • 17.Masur H, Michelis MA, Green JB, et al. An outbreak of community-acquired Pneumocystic carinii pneumonia. Initial manifestation of cellular immune dysfunction. N Engl J Med. 1981;305:1431. doi: 10.1056/NEJM198112103052402. [DOI] [PubMed] [Google Scholar]
  • 18.Mavligit G, Talpaz M, Hsia FT et al. (1984) Chronic immune stimulation by sperm allo-antigens: Support for the hypothesis that spermatozoa induce immune dysregulation in homosexual males. N Engl J Med (in press) [DOI] [PubMed]
  • 19.Reuben JM, Hersh EM, Mansell PW, et al. Immunological characterization of homosexual males. Cancer Res. 1983;43:897. [PubMed] [Google Scholar]
  • 20.Siegal FP, Lopez C, Hammer GS, et al. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med. 1981;305:1432. doi: 10.1056/NEJM198112103052403. [DOI] [PubMed] [Google Scholar]
  • 21.Wason S, Detsky AS, Platt OS, Lovejoy FH. Isobutyl nitrite toxicity by ingestion. Ann Intern Med. 1980;92:637. doi: 10.7326/0003-4819-92-5-637. [DOI] [PubMed] [Google Scholar]

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