Imidacloprid Exposure Suppresses Cytokine Production And Neutrophil Infiltration In Tlr2-Dependent Activation Of Rbl-2h3 Cells And Skin Inflammation Of Balb/C Mice

As the "first responders" of the immune system, mast cells immediately respond to invading pathogens via TLR2-mediated recognition of pathogens and play an important role in the host's immune responses required to clear the infection. Imidacloprid is a neonicotinoid agent that can suppress immune responses in mice. However, limited information is available on its impact on TLR-mediated mast cell activation at the beginning of an infection. In this study, the effects of imidacloprid on TLR2-activated rat mast cell/basophil cell line RBL-2H3 (RBL-2H3 cells) and TLR2-induced skin inflammation in BALB/c mice were determined, after which we measured the release of allergic mediators, Ca2+ influx, production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and neutrophil infiltration. The results showed that 10(-3) to 10(-5) M imidacloprid significantly decreased TNF-alpha and IL-6 production in TLR2-dependent activation of RBL-2H3 cells. Moreover, 10(-3) to 10(-4) M imidacloprid in 100 mu L of vehicle suppressed cytokine production and neutrophil infiltration in a TLR2-dependent skin inflammation model of BALB/c mice. Our work indicates that imidacloprid poses a possible health risk to hosts as it may inhibit the hosts' immune responses via the suppression of TLR2-mediated mast cell activation, leading to a less effective immune response in hosts at the beginning of an infection.