Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production

Evan M Hersh, J. M. Reuben, H. Bogerd, M. Rosenblum, M. Bielski, P. W. Mansell, A. Rios, G. R. Newell, G. Sonnenfeld

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The effects of the isobutyl nitrite sold as incense and the chemically pure compound on various in vitro parameters of leukocyte function were studied. This was done because of the potential relationship of isobutyl nitrite use to the opportunistic infection and Kaposi's sarcoma seen in homosexual men. Various concentrations of isobutyl nitrite dissolved in ethyl alcohol were added to various leukocyte cultures. The final added concentrations were 0.001 to 1.0%. Because of the poor solubility of the agent, the fluid concentrations were quite low after addition. Thus, the measured concentrations in the medium after preparation of 1% (v/v) solution were 0.45 mM at 1 hr, 0.04 mM at 24 hr, and 0.04 mM at 48 hr of incubation at 37° in 5% CO 2 in air. At the 1% added concentration, the agent lysed leukocytes and reduced viability from 95% to 21% in 24 hr. At an added concentration of 0.5% or below, cell count and viability were unaffected, but the agent inhibited in vitro lymphocyte blastogenic responses to phytohemagglutinin, pokeweed mitogen, and concanavalin A. It also inhibited natural killer cell activity to the K562 cell line, lymphocyte-mediated antibody-dependent cellular cytotoxicity to the CEM cell line, monocyte-mediated antibody-dependent cellular cytotoxicity to human red blood cells, and in vitro adherence and transformation of monocytes to macrophages. Inhibitory effects were greater than 90% at the 0.5% concentration and were still detectable at 0.01%. Chemically pure isobutyl nitrate and the form sold as incense had identical effects. The agent volatilized from the tissue culture medium at 37° so that its effect on cell viability was reduced about one-third after 24 hr and was gone by 48 hr. The agent inhibited leucine, uridine, and thymidine incorporation approximately equally. Within 2 hr of exposure to isobutyl nitrite, uridine and leucine incorporation were markedly inhibited. After 24 hr of exposure to the agent, the effects on various lymphocyte function parameters were not reversible. The thymidine incorporation of myeloid and solid tumor cell lines was also inhibited by the same concentrations of isobutyl nitrite which inhibited leukocyte functions. Induction of α,β-interferon by polyriboinosinic-polyribocytidylic acid in mouse embryo fibroblasts was inhibited by pretreatment of the cells with isobutyl nitrite. These data suggest that isobutyl nitrite has nonspecific cytotoxic activity for various cells in vitro and could have immunosuppressive effects on tissues exposed in vivo during its recreational use. We speculate that these immunosuppressive effects, combined with the ability of nitrites to convert amines to nitrosamines, may be related to the development of opportunistic infections and Kaposi's sarcoma in homosexuals who use this agent.

Original languageEnglish (US)
Pages (from-to)1365-1371
Number of pages7
JournalCancer Research
Volume43
Issue number3
StatePublished - 1983
Externally publishedYes

Fingerprint

Interferons
Leukocytes
Kaposi's Sarcoma
Uridine
Opportunistic Infections
Lymphocytes
Immunosuppressive Agents
Leucine
Thymidine
Monocytes
Cell Survival
Cell Line
Pokeweed Mitogens
Nitrosamines
K562 Cells
Antibodies
Phytohemagglutinins
Carbon Monoxide
Concanavalin A
Nitrites

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hersh, E. M., Reuben, J. M., Bogerd, H., Rosenblum, M., Bielski, M., Mansell, P. W., ... Sonnenfeld, G. (1983). Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production. Cancer Research, 43(3), 1365-1371.

Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production. / Hersh, Evan M; Reuben, J. M.; Bogerd, H.; Rosenblum, M.; Bielski, M.; Mansell, P. W.; Rios, A.; Newell, G. R.; Sonnenfeld, G.

In: Cancer Research, Vol. 43, No. 3, 1983, p. 1365-1371.

Research output: Contribution to journalArticle

Hersh, EM, Reuben, JM, Bogerd, H, Rosenblum, M, Bielski, M, Mansell, PW, Rios, A, Newell, GR & Sonnenfeld, G 1983, 'Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production', Cancer Research, vol. 43, no. 3, pp. 1365-1371.
Hersh, Evan M ; Reuben, J. M. ; Bogerd, H. ; Rosenblum, M. ; Bielski, M. ; Mansell, P. W. ; Rios, A. ; Newell, G. R. ; Sonnenfeld, G. / Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production. In: Cancer Research. 1983 ; Vol. 43, No. 3. pp. 1365-1371.
@article{4dc3ddbc194e4a27be7841efdf04f372,
title = "Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production",
abstract = "The effects of the isobutyl nitrite sold as incense and the chemically pure compound on various in vitro parameters of leukocyte function were studied. This was done because of the potential relationship of isobutyl nitrite use to the opportunistic infection and Kaposi's sarcoma seen in homosexual men. Various concentrations of isobutyl nitrite dissolved in ethyl alcohol were added to various leukocyte cultures. The final added concentrations were 0.001 to 1.0{\%}. Because of the poor solubility of the agent, the fluid concentrations were quite low after addition. Thus, the measured concentrations in the medium after preparation of 1{\%} (v/v) solution were 0.45 mM at 1 hr, 0.04 mM at 24 hr, and 0.04 mM at 48 hr of incubation at 37° in 5{\%} CO 2 in air. At the 1{\%} added concentration, the agent lysed leukocytes and reduced viability from 95{\%} to 21{\%} in 24 hr. At an added concentration of 0.5{\%} or below, cell count and viability were unaffected, but the agent inhibited in vitro lymphocyte blastogenic responses to phytohemagglutinin, pokeweed mitogen, and concanavalin A. It also inhibited natural killer cell activity to the K562 cell line, lymphocyte-mediated antibody-dependent cellular cytotoxicity to the CEM cell line, monocyte-mediated antibody-dependent cellular cytotoxicity to human red blood cells, and in vitro adherence and transformation of monocytes to macrophages. Inhibitory effects were greater than 90{\%} at the 0.5{\%} concentration and were still detectable at 0.01{\%}. Chemically pure isobutyl nitrate and the form sold as incense had identical effects. The agent volatilized from the tissue culture medium at 37° so that its effect on cell viability was reduced about one-third after 24 hr and was gone by 48 hr. The agent inhibited leucine, uridine, and thymidine incorporation approximately equally. Within 2 hr of exposure to isobutyl nitrite, uridine and leucine incorporation were markedly inhibited. After 24 hr of exposure to the agent, the effects on various lymphocyte function parameters were not reversible. The thymidine incorporation of myeloid and solid tumor cell lines was also inhibited by the same concentrations of isobutyl nitrite which inhibited leukocyte functions. Induction of α,β-interferon by polyriboinosinic-polyribocytidylic acid in mouse embryo fibroblasts was inhibited by pretreatment of the cells with isobutyl nitrite. These data suggest that isobutyl nitrite has nonspecific cytotoxic activity for various cells in vitro and could have immunosuppressive effects on tissues exposed in vivo during its recreational use. We speculate that these immunosuppressive effects, combined with the ability of nitrites to convert amines to nitrosamines, may be related to the development of opportunistic infections and Kaposi's sarcoma in homosexuals who use this agent.",
author = "Hersh, {Evan M} and Reuben, {J. M.} and H. Bogerd and M. Rosenblum and M. Bielski and Mansell, {P. W.} and A. Rios and Newell, {G. R.} and G. Sonnenfeld",
year = "1983",
language = "English (US)",
volume = "43",
pages = "1365--1371",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production

AU - Hersh, Evan M

AU - Reuben, J. M.

AU - Bogerd, H.

AU - Rosenblum, M.

AU - Bielski, M.

AU - Mansell, P. W.

AU - Rios, A.

AU - Newell, G. R.

AU - Sonnenfeld, G.

PY - 1983

Y1 - 1983

N2 - The effects of the isobutyl nitrite sold as incense and the chemically pure compound on various in vitro parameters of leukocyte function were studied. This was done because of the potential relationship of isobutyl nitrite use to the opportunistic infection and Kaposi's sarcoma seen in homosexual men. Various concentrations of isobutyl nitrite dissolved in ethyl alcohol were added to various leukocyte cultures. The final added concentrations were 0.001 to 1.0%. Because of the poor solubility of the agent, the fluid concentrations were quite low after addition. Thus, the measured concentrations in the medium after preparation of 1% (v/v) solution were 0.45 mM at 1 hr, 0.04 mM at 24 hr, and 0.04 mM at 48 hr of incubation at 37° in 5% CO 2 in air. At the 1% added concentration, the agent lysed leukocytes and reduced viability from 95% to 21% in 24 hr. At an added concentration of 0.5% or below, cell count and viability were unaffected, but the agent inhibited in vitro lymphocyte blastogenic responses to phytohemagglutinin, pokeweed mitogen, and concanavalin A. It also inhibited natural killer cell activity to the K562 cell line, lymphocyte-mediated antibody-dependent cellular cytotoxicity to the CEM cell line, monocyte-mediated antibody-dependent cellular cytotoxicity to human red blood cells, and in vitro adherence and transformation of monocytes to macrophages. Inhibitory effects were greater than 90% at the 0.5% concentration and were still detectable at 0.01%. Chemically pure isobutyl nitrate and the form sold as incense had identical effects. The agent volatilized from the tissue culture medium at 37° so that its effect on cell viability was reduced about one-third after 24 hr and was gone by 48 hr. The agent inhibited leucine, uridine, and thymidine incorporation approximately equally. Within 2 hr of exposure to isobutyl nitrite, uridine and leucine incorporation were markedly inhibited. After 24 hr of exposure to the agent, the effects on various lymphocyte function parameters were not reversible. The thymidine incorporation of myeloid and solid tumor cell lines was also inhibited by the same concentrations of isobutyl nitrite which inhibited leukocyte functions. Induction of α,β-interferon by polyriboinosinic-polyribocytidylic acid in mouse embryo fibroblasts was inhibited by pretreatment of the cells with isobutyl nitrite. These data suggest that isobutyl nitrite has nonspecific cytotoxic activity for various cells in vitro and could have immunosuppressive effects on tissues exposed in vivo during its recreational use. We speculate that these immunosuppressive effects, combined with the ability of nitrites to convert amines to nitrosamines, may be related to the development of opportunistic infections and Kaposi's sarcoma in homosexuals who use this agent.

AB - The effects of the isobutyl nitrite sold as incense and the chemically pure compound on various in vitro parameters of leukocyte function were studied. This was done because of the potential relationship of isobutyl nitrite use to the opportunistic infection and Kaposi's sarcoma seen in homosexual men. Various concentrations of isobutyl nitrite dissolved in ethyl alcohol were added to various leukocyte cultures. The final added concentrations were 0.001 to 1.0%. Because of the poor solubility of the agent, the fluid concentrations were quite low after addition. Thus, the measured concentrations in the medium after preparation of 1% (v/v) solution were 0.45 mM at 1 hr, 0.04 mM at 24 hr, and 0.04 mM at 48 hr of incubation at 37° in 5% CO 2 in air. At the 1% added concentration, the agent lysed leukocytes and reduced viability from 95% to 21% in 24 hr. At an added concentration of 0.5% or below, cell count and viability were unaffected, but the agent inhibited in vitro lymphocyte blastogenic responses to phytohemagglutinin, pokeweed mitogen, and concanavalin A. It also inhibited natural killer cell activity to the K562 cell line, lymphocyte-mediated antibody-dependent cellular cytotoxicity to the CEM cell line, monocyte-mediated antibody-dependent cellular cytotoxicity to human red blood cells, and in vitro adherence and transformation of monocytes to macrophages. Inhibitory effects were greater than 90% at the 0.5% concentration and were still detectable at 0.01%. Chemically pure isobutyl nitrate and the form sold as incense had identical effects. The agent volatilized from the tissue culture medium at 37° so that its effect on cell viability was reduced about one-third after 24 hr and was gone by 48 hr. The agent inhibited leucine, uridine, and thymidine incorporation approximately equally. Within 2 hr of exposure to isobutyl nitrite, uridine and leucine incorporation were markedly inhibited. After 24 hr of exposure to the agent, the effects on various lymphocyte function parameters were not reversible. The thymidine incorporation of myeloid and solid tumor cell lines was also inhibited by the same concentrations of isobutyl nitrite which inhibited leukocyte functions. Induction of α,β-interferon by polyriboinosinic-polyribocytidylic acid in mouse embryo fibroblasts was inhibited by pretreatment of the cells with isobutyl nitrite. These data suggest that isobutyl nitrite has nonspecific cytotoxic activity for various cells in vitro and could have immunosuppressive effects on tissues exposed in vivo during its recreational use. We speculate that these immunosuppressive effects, combined with the ability of nitrites to convert amines to nitrosamines, may be related to the development of opportunistic infections and Kaposi's sarcoma in homosexuals who use this agent.

UR - http://www.scopus.com/inward/record.url?scp=0020686621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020686621&partnerID=8YFLogxK

M3 - Article

C2 - 6186374

AN - SCOPUS:0020686621

VL - 43

SP - 1365

EP - 1371

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 3

ER -