Di-isononyl phthalate (DINP) is one of the most widely used new plasticizers. Several studies have suggested that exposure to DINP may be involved in the occurrence and development of allergic asthma, and that the synergistic effect of DINP combined with ovalbumin (OVA) is a possible route to promote an immune response. However, safety data for DINP has been relatively scarce. Some studies have shown that there is a possible link between the interleukin-31(IL-31)/transient receptor potential cation channel vanillic acid subfamily member 1 (TRPV1) pathway and allergic asthma. This study was designed to determine the effects of OVA/DINP exposure on airway reactivity, and to elucidate the role of the IL-31/TRPV1 pathway in DINP-induced allergic asthma. Experiments to determine these effects were conducted after 28 days of combined exposure, and a subsequent challenge with aerosolized ovalbumin for one week. We measured airway hyper-responsiveness (AHR), examined lung tissue pathology, Th1/Th2 cytokines and IL-31/TRPV1 pathway biomarkers. We found that dermal exposure to DINP combined with OVA could induce AHR, and aggravate airway wall remodeling, and that this deterioration was concomitant with increased secretion of immunoglobulin-E (Ig-E) and Th2 cytokines. The data also showed that DINP could increase the levels of IL-31 and TRPV1. Administration of the IL-31/TPPV1 pathway antagonists (SB-431542 and CZP) to the DIDP-treated allergic asthma mice restored these biochemical parameters to within normal levels, and resulted in less damage in the lung. Overall, these results suggest that the IL-31/TPPV1 pathway is involved in DIDP-induced allergic asthma.
 

Di-isononyl phthalate; allergic asthma; TRPV1; IL-31;