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.
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.
Duramad
Paurene
P
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California 94720, USA.
Tager
Ira B
IB
Leikauf
John
J
Eskenazi
Brenda
B
Holland
Nina T
NT
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
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