title: Immunomodulatory effects of the fungicide Mancozeb in agricultural workers.
abstract: Available data suggest that ethylenebisdithiocarbamates (EBDCs) may have immunomodulatory effects. This study aimed to investigate the immunological profile of farmers exposed to Mancozeb, an EBDC fungicide, through the determination of several serum, cellular, and functional immune parameters. Twenty-six healthy subjects entered the study, 13 vineyards exposed to Mancozeb and 13 unexposed controls. Exposure was assessed through the determination of ethylentiourea (ETU) in urine. Complete and differential blood count, serum immunoglobulins, complement fractions, autoantibodies, lymphocyte subpopulations, proliferative response to mitogens, natural killer (NK) activity, and cytokine production were measured. Post-exposure samples showed ETU urine concentration significantly higher than pre-exposure and control groups. A significant increase in CD19+ cells, both percentage and absolute number, and a significant decrease in the percentage of CD25+ cells were found in post-exposure samples compared to controls. A statistically significant increase in the proliferative response to phorbol myristate acetate plus ionomycin (PMA + ionomycin) was observed in the post-exposure group compared to controls and baseline, while a significant reduction in LPS-induced TNF-alpha release in post-exposure samples was observed. Overall, our results suggest that low-level exposure to Mancozeb has slight immunomodulatory effects, and point out a method adequate to reveal immune-modifications in workers occupationally exposed to potential immunotoxic compounds, based on a whole blood assay.
authors.affiliation: Laboratory of Toxicology, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Corsini
authors.forename: Sarah
authors.initials: S
authors.lastname: Birindelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Fustinoni
authors.forename: Gioia
authors.initials: G
authors.lastname: De Paschale
authors.forename: Teresa
authors.initials: T
authors.lastname: Mammone
authors.forename: Sara
authors.initials: S
authors.lastname: Visentin
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; D001772:Blood Cell Count; D002273:Carcinogens / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005031:Ethylenethiourea / Q000378:metabolism; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007136:Immunoglobulins / Q000032:analysis; D007155:Immunologic Factors; D007694:Killer Cells, Natural / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008344:Maneb / Q000633:toxicity*; D008875:Middle Aged; D016273:Occupational Exposure; D015038:Zineb / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D016207:Cytokines; D005659:Fungicides, Industrial; D007136:Immunoglobulins; D007155:Immunologic Factors; D008344:Maneb; D005031:Ethylenethiourea; D007770:L-Lactate Dehydrogenase; C013099:mancozeb; D015038:Zineb