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Title: Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure

Abstract

Propanil, 3,4-dichloropropionanilide, a commonly used herbicide, has been shown to induce effects on the mouse immune system. The aim of this study was to assess the immunotoxicity of propanil in occupationally exposed agricultural workers and to characterize its molecular mechanism of action. Seven agricultural workers intermittently exposed to propanil and 7 healthy matched controls entered the study. Data were collected through physical examination, and laboratory investigations addressed at the main serum, cellular, and functional immune parameters. The levels of exposure were assessed by determining the urine concentration of the major propanil metabolite, 3,4-dichloroaniline. The investigation of serum, cellular, and functional immune parameters suggested that propanil exposure results in a modest immunomodulatory effect, characterized by an increase in the plasma level of IgG{sub 1} and in LPS-induced IL-6 release and, by a reduction in PHA-induced IL-10 and IFN release, associated with a reduced IFN/IL-4 ratio. As observed, following in vivo exposure, in vitro treatment of human peripheral blood leukocytes with propanil resulted in a dose-dependent reduction in PHA-induced IFN-gamma and IL-10 production, while LPS-induced TNF-{alpha} production was not affected indicating a direct effect of propanil on selected immune parameters. We demonstrated that propanil interfering with PHA-induced intracellular calcium increase modulated IL-10more » and IFN-gamma transcription and translation, which indicates that propanil acts on early events triggered by PHA. Overall, our results suggest that human exposure to propanil has slight immunomodulatory effects, and point out that the inhibition of the PHA-induced intracellular calcium rise is an important target of propanil. These findings improve our understanding of the mechanism underlying propanil-induced immunotoxicity.« less

Authors:
 [1];  [1];  [1];  [2];  [3];  [3];  [1];  [1];  [4];  [1];  [1];  [1];  [4]
  1. Laboratory of Toxicology, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan (Italy)
  2. International Centre for Pesticides and Health Risk Prevention, Hospital L. Sacco, Milan (Italy)
  3. S. Maugeri Foundation, IRCCS, Pavia (Italy)
  4. Department of Occupational Health of University of Milan, S. Paolo Hospital Unit, Milan (Italy)
Publication Date:
OSTI Identifier:
20976987
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 222; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2007.04.017; PII: S0041-008X(07)00208-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CALCIUM; HERBICIDES; HUMAN POPULATIONS; IN VITRO; IN VIVO; INHIBITION; LEUKOCYTES; MICE; TRANSCRIPTION; URINE

Citation Formats

Corsini, Emanuela, Codeca, Ilaria, Mangiaratti, Simona, Birindelli, Sarah, Minoia, Claudio, Turci, Roberta, Viviani, Barbara, Facchi, Alessandra, Vitelli, Nora, Lucchi, Laura, Galli, Corrado L, Marinovich, Marina, and Colosio, Claudio. Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure. United States: N. p., 2007. Web. doi:10.1016/j.taap.2007.04.017.
Corsini, Emanuela, Codeca, Ilaria, Mangiaratti, Simona, Birindelli, Sarah, Minoia, Claudio, Turci, Roberta, Viviani, Barbara, Facchi, Alessandra, Vitelli, Nora, Lucchi, Laura, Galli, Corrado L, Marinovich, Marina, & Colosio, Claudio. Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure. United States. https://doi.org/10.1016/j.taap.2007.04.017
Corsini, Emanuela, Codeca, Ilaria, Mangiaratti, Simona, Birindelli, Sarah, Minoia, Claudio, Turci, Roberta, Viviani, Barbara, Facchi, Alessandra, Vitelli, Nora, Lucchi, Laura, Galli, Corrado L, Marinovich, Marina, and Colosio, Claudio. Sun . "Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure". United States. https://doi.org/10.1016/j.taap.2007.04.017.
@article{osti_20976987,
title = {Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure},
author = {Corsini, Emanuela and Codeca, Ilaria and Mangiaratti, Simona and Birindelli, Sarah and Minoia, Claudio and Turci, Roberta and Viviani, Barbara and Facchi, Alessandra and Vitelli, Nora and Lucchi, Laura and Galli, Corrado L and Marinovich, Marina and Colosio, Claudio},
abstractNote = {Propanil, 3,4-dichloropropionanilide, a commonly used herbicide, has been shown to induce effects on the mouse immune system. The aim of this study was to assess the immunotoxicity of propanil in occupationally exposed agricultural workers and to characterize its molecular mechanism of action. Seven agricultural workers intermittently exposed to propanil and 7 healthy matched controls entered the study. Data were collected through physical examination, and laboratory investigations addressed at the main serum, cellular, and functional immune parameters. The levels of exposure were assessed by determining the urine concentration of the major propanil metabolite, 3,4-dichloroaniline. The investigation of serum, cellular, and functional immune parameters suggested that propanil exposure results in a modest immunomodulatory effect, characterized by an increase in the plasma level of IgG{sub 1} and in LPS-induced IL-6 release and, by a reduction in PHA-induced IL-10 and IFN release, associated with a reduced IFN/IL-4 ratio. As observed, following in vivo exposure, in vitro treatment of human peripheral blood leukocytes with propanil resulted in a dose-dependent reduction in PHA-induced IFN-gamma and IL-10 production, while LPS-induced TNF-{alpha} production was not affected indicating a direct effect of propanil on selected immune parameters. We demonstrated that propanil interfering with PHA-induced intracellular calcium increase modulated IL-10 and IFN-gamma transcription and translation, which indicates that propanil acts on early events triggered by PHA. Overall, our results suggest that human exposure to propanil has slight immunomodulatory effects, and point out that the inhibition of the PHA-induced intracellular calcium rise is an important target of propanil. These findings improve our understanding of the mechanism underlying propanil-induced immunotoxicity.},
doi = {10.1016/j.taap.2007.04.017},
url = {https://www.osti.gov/biblio/20976987}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 222,
place = {United States},
year = {2007},
month = {7}
}