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(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.
authors.affiliation: Laboratory of Toxicology, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. emanuela.corsini@unimi.it
authors.forename: Emanuela
authors.initials: E
authors.lastname: Corsini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Codecà
authors.forename: Simona
authors.initials: S
authors.lastname: Mangiaratti
authors.forename: Sarah
authors.initials: S
authors.lastname: Birindelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Minoia
authors.forename: Roberta
authors.initials: R
authors.lastname: Turci
authors.forename: Barbara
authors.initials: B
authors.lastname: Viviani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Facchi
authors.forename: Nora
authors.initials: N
authors.lastname: Vitelli
authors.forename: Laura
authors.initials: L
authors.lastname: Lucchi
authors.forename: Corrado L
authors.initials: CL
authors.lastname: Galli
authors.forename: Marina
authors.initials: M
authors.lastname: Marinovich
authors.forename: Claudio
authors.initials: C
authors.lastname: Colosio
mesh_terms: D000328:Adult; D000383:Agriculture; D000814:Aniline Compounds / Q000652:urine; D002118:Calcium / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006540:Herbicides / Q000506:poisoning; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007155:Immunologic Factors / Q000506:poisoning*; D007558:Italy; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis; D010808:Physical Examination; D010835:Phytohemagglutinins / Q000494:pharmacology; D011411:Propanil / Q000506:poisoning*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011795:Surveys and Questionnaires
chemical_list: D000814:Aniline Compounds; D016207:Cytokines; D006540:Herbicides; D007136:Immunoglobulins; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D012333:RNA, Messenger; C014464:3,4-dichloroaniline; D011411:Propanil; D002118:Calcium