Immunosuppressive effect of isopropanol: down-regulation of cytokine production results from the alteration of discrete transcriptional pathways in activated lymphocytes.
Isopropanol (IPA) is widely used in household applications and constitutes a leading cause of acute alcohol intoxication second only to ethanol. Although the effects of ethanol on the immune system have been extensively studied, far fewer data are available on IPA. Given the structural similarity between the two molecules, we hypothesized that IPA could as well have immunomodulatory properties. We report here that acute IPA exposure is detrimental to human T lymphocyte and NK cell activity in vitro in concentrations as low as 0.08-0.16% (13-26 mM). IPA treatment did not affect receptor-mediated early signaling but had a reproducible and dose-dependent effect on the nuclear translocation of NFAT and AP-1. Furthermore, we show in a model of acute IPA intoxication that animals became immunosuppressed as judged by their reduced ability to release IL-2 and IFN-gamma in the serum in response to staphylococcal enterotoxin B. This effect was also associated to the down-regulation of TNF-alpha production and was sufficiently strong to rescue susceptible animals from enterotoxin-induced toxic shock. Our results suggest that IPA is potentially immunosuppressive to the adaptive and innate immune system and have broad significance given the exposure of the general population to this ubiquitous chemical.
Désy
Olivier
O
Laval University Cancer Research Center, Quebec City, Quebec, Canada.
Carignan
Damien
D
Caruso
Manuel
M
de Campos-Lima
Pedro O
PO
D019840:2-Propanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012772:Shock, Septic / Q000097:blood / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*
D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D019840:2-Propanol