Many allergic diseases and neutrophilic inflammations are multifactorial. The susceptibility to these diseases is caused by the interaction between genetic and environmental factors. However, a significant increase in the prevalence of these diseases has been observed in recent decades, possibly due to environmental factors. In the present study, we examined diazinon (DZN) as an agricultural organophosphate pesticide to identify their immunomodulatory effects as a possible environmental factor. We measured the levels of IFN-γ, IL-4/5, IL-17, IL-5 and IL-8 as indicators for Th1, Th2 and Th17 responses and eosinophilic and neutrophilic inflammation, respectively. We found that DZN increases the production of IL-8 from a human acute monocytic leukemia cell line (THP-1). Furthermore, the IL-8 production was increased in human macrophages stimulated with DZN. A 5-hydroxytryptamine (5-HT) receptor antagonist or a protein kinase C (PKC) inhibitor was able to suppress the IL-8 production from THP-1 cells stimulated by DZN. These observations suggest that DZN binds to 5-HTR in human monocytic cells, thereby producing IL-8 via PKC activation. DZN may exacerbate human neutrophilic inflammation.
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