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Immunosuppressive Effect of Isopropanol: Down-Regulation of Cytokine Production Results from the Alteration of Discrete Transcriptional Pathways in Activated Lymphocytes¹

Laval University Cancer Research Center, Quebec City, Quebec, Canada

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- in the serum in response to staphylococcal enterotoxin B. This effect was also associated to the down-regulation of TNF- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Sciences and Engineering Research Council of Canada and the Canada Foundation for Innovation.

² Address correspondence and reprint requests to Dr. Pedro O. de Campos-Lima, Laval University Cancer Research Center, McMahon Street 9, Quebec City, QC, G1R 2J6, Canada.

³ Abbreviations used in this paper: IPA, isopropanol, isopropyl alcohol, 2-propanol; SEB, staphylococcal enterotoxin B; poly(IC), polyinosinic-polycytidylic acid; h (in combination), human; m (in combination), murine.