Perinatal Exposure to Insecticide Methamidophos Suppressed Production of Proinflammatory Cytokines Responding to Virus Infection in Lung Tissues in Mice

Abstract

Methamidophos, a representative organophosphate insecticide, is regulated because of its severe neurotoxicity, but it is suspected of contaminating agricultural foods in many countries due to illicit use. To reveal unknown effects of methamidophos on human health, we evaluated the developmental immunotoxicity of methamidophos using a respiratory syncytial virus (RSV) infection mouse model. Pregnant mice were exposed to methamidophos (10 or 20 ppm) in their drinking water from gestation day 10 to weaning on postnatal day 21. Offsprings born to these dams were intranasally infected with RSV. The levels of interleukin-6 (IL-6) and interferon-gamma in the bronchoalveolar lavage fluids after infection were significantly decreased in offspring mice exposed to methamidophos. Treatment with methamidophos did not affect the pulmonary viral titers but suppressed moderately the inflammation of lung tissues of RSV-infected offspring, histopathologically. DNA microarray analysis revealed that gene expression of the cytokines in the lungs of offspring mice exposed to 20 ppm of methamidophos was apparently suppressed compared with the control. Methamidophos did not suppress IL-6 production in RSV-infected J774.1 cell cultures. Thus, exposure of the mother to methamidophos during pregnancy and nursing was suggested to cause an irregular immune response in the lung tissues in the offspring mice.

Effects of Chlorpyrifos on Serine Hydrolase Activities, Lipid Mediators, and Immune Responses in Lungs of Neonatal and Adult Mice

“…51 On the other hand, mice exposed to methamidophos in drinking water from gestation day 10 to postnatal day 21 had lower levels of IL-6 following infection with respiratory syncytial virus. 52 However, on the whole, there is a paucity of laboratory data that have examined the relationship between pesticides and lung health.…”

“…One study found no difference in the extent of LPS-induced lung inflammation following 90-day oral exposures of mice to ethion (an OP insecticide) and vehicle . On the other hand, mice exposed to methamidophos in drinking water from gestation day 10 to postnatal day 21 had lower levels of IL-6 following infection with respiratory syncytial virus . However, on the whole, there is a paucity of laboratory data that have examined the relationship between pesticides and lung health.…”

“…Given that (i) Ces enzymes are present in both pulmonary macrophages and lung epithelial cells and can metabolize lipid mediators, ,, (ii) alveolar macrophages possess Ces activity capable of hydrolyzing pesticides, and (iii) evidence exists that pesticides affect viral respiratory immune responses, we opted to explore the ability of CPF to alter lung immune responses through a mechanism involving the eCB system in a murine model of LPS-induced inflammation. Further justification for examining lung Ces enzymes in the context of CPF exposure and inflammation comes from our observations that adult female Ces1d –/– mice exhibit heightened levels of lung Il6 mRNA compared to their WT counterparts following an LPS challenge .…”

Organophosphate-Pesticide-Mediated Immune Response Modulation in Invertebrates and Vertebrates

“…Perinatal exposure to methamidophos interferes with neutrophil recruitment through IL-6 and interferon in response to the respiratory syncytial virus (RSV) in the lung tissue in the offspring generation of mice [ 99 ]. In addition, 2,2-Dichlorovinyl dimethyl phosphate (DDVP) induced inhibition of NK, limphokine-activated killer cells (LAK), and Cytotoxic T lymphocytes (CTL) activities in KO mice, through the impairment of the FasL/Fas pathway-associated phenomenon [ 100 ].…”

Perinatal exposure to tetrabromobisphenol A (TBBPA), a brominated flame retardant, exacerbated the pneumonia in respiratory syncytial virus (RSV)-infected offspring mice

“…To evaluate the immunotoxicity of environmental chemicals including BFRs, we established a novel assay system using a murine model of RSV infection because the severity of RSV infection reflects the condition of the host immunity (Watanabe et al, 2008a). We subsequently demonstrated that decabrominated diphenyl ether (DBDE), a BFR, and methamidophos, a representative organophosphate insecticide, caused developmental immunotoxicity (Watanabe et al, 2008b) and suppressed the production of proinflammatory cytokines using this model (Watanabe et al, 2013), respectively. In addition, we also revealed that titanium dioxide caused immune disorder and then exacerbated pneumonia in RSV-infected mice (Hashiguchi et al, 2015).…”