title: Expression of Th1/Th2 cytokines in human blood after in vitro treatment with chlorpyrifos, and its metabolites, in combination with endotoxin LPS and allergen Der p1.
abstract: Exposure to organophosphate (OP) pesticides has been associated with respiratory symptoms and may be related to asthma; however, few studies have examined the molecular basis for these associations. Asthma and allergic disorders are characterized by elevated Th2 cytokines (IL-4, IL-5, IL-13), whereas the chronic inflammatory response in asthmatic airways is maintained by Th1 cytokine IFN-gamma. The goal of this in vitro study was to examine the effects of OP chlorpyrifos (CPF), and its metabolites chlorpyrifos-oxon (CPO) and 3,5,6-trichloro-2-pyridinol (TCP), singly, and in combination with endotoxin lipopolysaccharide (LPS) or house dust mite Dermatophagoides pteronyssinus (Der p1) allergen, on expression of IFN-gamma and IL-4, Th1 and Th2 signature cytokines, respectively. Cytokine expression was measured by ELISA and flow cytometry. Human blood cultures were treated with CPF/CPO/TCP (1-1000 microg ml(-1)) and LPS (1.5-2.5 microg ml(-1)) or Der p1 (200 AU ml(-1)) and supernatants were collected at 48 h. Pesticides CPF, CPO and TCP did not induce cytokine expression in vitro, while LPS and Der p1 induced IFN-gamma and IL-4 expression, respectively. Whole blood cultures treated with low doses of CPO (1 and 10 microg ml(-1)), in combination with LPS, expressed higher levels of IFN-gamma than LPS alone (P < 0.05). While CPO increased LPS-dependent induction of IFN-gamma, CPO treatment did not alter Der p1 induction of IL-4. The interaction between CPO and LPS, which results in an increased type 1 immune response, should be investigated further, particularly since the combination of OP pesticides and endotoxin is common in rural, agricultural communities.
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California 94720, USA.
authors.forename: Paurene
authors.initials: P
authors.lastname: Duramad
authors.forename: Ira B
authors.initials: IB
authors.lastname: Tager
authors.forename: John
authors.initials: J
authors.lastname: Leikauf
authors.forename: Brenda
authors.initials: B
authors.lastname: Eskenazi
authors.forename: Nina T
authors.initials: NT
authors.lastname: Holland
mesh_terms: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000031:analogs & derivatives* / Q000633:toxicity; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides; D011728:Pyridones / Q000633:toxicity*; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; C508598:IL4 protein, human; D007306:Insecticides; D008070:Lipopolysaccharides; D011728:Pyridones; D015847:Interleukin-4; C009618:O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate; C012587:3,5,6-trichloro-2-pyridinol; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1; D004390:Chlorpyrifos