Chlorpyrifos, but not diazinon, potentiates airway hyperreactivity in sensitized guinea pigs

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Background: Organophosphorus pesticides (OPs) are commonly used on crops and livestock. We have shown that the OPs parathion, chlorpyrifos, and diazinon cause airway hyperreactivity in guinea pigs at concentrations below the threshold for inducing toxicity via acetylcholinesterase inhibition. Furthermore, ovalbumin sensitization potentiated parathion-induced airway hyperreactivity in an interleukin-5 (IL-5) dependent manner. Objective: To determine whether prior sensitization also potentiates chlorpyrifos and diazinon induced airway hyperreactivity and whether IL-5 mediates potentiation in sensitized animals. Methods: Guinea pigs were sensitized to ovalbumin, and 21 days later, exposed to 70 mg/kg chlorpyrifos or 75 mg/kg diazinon (s.c.). Airway physiology was measured 24 h later. In some animals, antibody to IL-5 (240 µg/kg) was administered 3 days prior the OP. Results: Chlorpyrifos and diazinon each caused airway hyperreactivity in non-sensitized guinea pigs. Sensitization significantly potentiated chlorpyrifos-induced, but not diazinon-induced, airway hyperreactivity. Pretreatment with antibody to IL-5 prevented chlorpyrifos-induced airway hyperreactivity only in sensitized animals. Antibody to IL-5 did not significantly inhibit airway hyperreactivity in sensitized animals treated with diazinon. Conclusion: Chlorpyrifos and diazinon each cause airway hyperreactivity. Chlorpyrifos-induced airway hyperreactivity was significantly potentiated and IL-5 dependent in sensitized guinea pigs whereas diazinon-induced hyperreactivity was not. Thus, OP-induced airway hyperreactivity is mediated by different mechanisms, dependent on sensitization status, which may influence therapeutic approaches.