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
✍ Scribed by Paurene Duramad; Ira B. Tager; John Leikauf; Brenda Eskenazi; Nina T. Holland
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 297 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0260-437X
- DOI
- 10.1002/jat.1162
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✦ Synopsis
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‐γ. 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‐γ 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 µg ml^−1^) and LPS (1.5–2.5 µg 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‐γ and IL‐4 expression, respectively. Whole blood cultures treated with low doses of CPO (1 and 10 µg ml^−1^), in combination with LPS, expressed higher levels of IFN‐γ than LPS alone (P < 0.05). While CPO increased LPS‐dependent induction of IFN‐γ, 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. Copyright © 2006 John Wiley & Sons, Ltd.