Effects of prior oral exposure to combinations of environmental immunosuppressive agents on ovalbumin allergen-induced allergic airway inflammation in Balb/c mice

Abstract

Humans are exposed daily to multiple environmental chemicals in the atmosphere, in food, and in commercial products. Therefore, hazard identification and risk management must account for exposure to chemical mixtures. The objective of the study reported here was to investigate the effects of combinations of three well-known environmental immunotoxic chemicals - methoxychlor (MXC), an organochlorine compound; parathion (PARA), an organophosphate compound; and piperonyl butoxide (PBO), an agricultural insecticide synergist - by using a mouse model of ovalbumin (OVA)-induced allergic airway inflammation. Four-week-old Balb/c mice were exposed orally to either one or two of the environmental immunotoxic chemicals for five consecutive days, prior to intraperitoneal sensitization with OVA and an inhalation challenge. We assessed IgE levels in serum, B-cell counts, and cytokine production in hilar lymph nodes, and differential cell counts and levels of related chemokines in bronchoalveolar lavage fluid (BALF). Mice treated with MXC + PARA or PBO + MXC showed marked increases in serum IgE, IgE-positive B-cells and cytokines in lymph nodes, and differential cell counts and related chemokines in BALF compared with mice that received the vehicle control or the corresponding individual test substances. These results suggest that simultaneous exposure to multiple environmental chemicals aggravates allergic airway inflammation more than exposure to individual chemicals. It is expected that the results of this study will help others in their evaluation of immunotoxic combinational effects when conducting assessments of the safety of environmental/occupational chemicals.

Effect of prenatal exposure to combined immunosuppressive agrochemicals in a mouse model of allergic airway inflammation

“…The effect of short-term oral exposure to a combination of environmental immunotoxic chemicals on the adaptive immune system and allergic airway inflammation has been recently investigated by our group [7, 11]. Nishino et al .…”

“…Fukuyama et al . [7] further examined the effect using a mouse model of allergic airway inflammation. MXC + PARA and PBO + MXC combinations induced a significant increase in allergic airway inflammation compared to that induced by exposure to the individual chemicals, as indicated by the IgE responses, eosinophil counts, and levels of pro-inflammatory chemokines and cytokines.…”

“…This study aimed to provide information about the developmental effect of oral exposure to a combination of multiple chemicals. We showed in a recent study that oral exposure to a combination of the organochlorine agent MXC and organophosphorus agent PARA synergistically suppresses the adaptive immune system [11] and aggravates allergic airway inflammation in mice [7]. However, immune responses are strongly affected by the age of the animal, and MXC and PARA are also easily transported from mother to juvenile through the placenta and breast milk.…”