| 16871525 |
Duramad P, Tager IB, Leikauf J, Eskenazi B, Holland NT: 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. J Appl Toxicol. 2006 Sep-Oct;26(5):458-65.
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. |
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