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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(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.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Corsini E,Codecà I,Mangiaratti S,Birindelli S,Minoia C,Turci R,Viviani B,Facchi A,Vitelli N,Lucchi L,Galli CL,Marinovich M,Colosio C

doi

10.1016/j.taap.2007.04.017

subject

Has Abstract

pub_date

2007-07-15 00:00:00

pages

202-10

issue

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(07)00208-6

journal_volume

222

pub_type

临床试验,杂志文章

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