Immunomodulatory properties of the endocrine disruptor tolylfluanid and its effect on the corticosterone and cytokine level in male mice : a preliminary study

Abstract

Pesticides are specific chemicals that can be used alone or as mixtures to kill, destroy, and suppress normal life cycle of pests and unwanted weeds. The association between pesticides and elevated human health risks earned increased attention among scientists and health care providers. Since direct contact with high doses of poisonous chemicals on daily basis might cause serious health deteriorations, the occupational exposure to pesticides is of special medical concern. The most health problematic pesticide group is fungicides. Tolylfluanid (TF) is a polyvalent sulfamide fungicide used extensively in agriculture to prevent fungal infestation as a protective mode. Recently, tolylfluanid was characterized as so called Endocrine Disrupting Chemical (EDC). EDCs are synthetic chemicals that mimic natural hormones and thus may pose serious risks for human health. In fact, environmental pollutants (e. g. fungicides) including EDCs have strong immunomodulatory properties mediated trough an endocrine-disrupting mechanism. Many pesticides including TF have been identified as endocrine-disrupting chemicals due to their ability to interfere with hormone receptor or glucocorticoid receptors (GR) as hormone agonist or antagonist. Furthermore, TF can mimic corticosterone hormone (major glucocorticoid in rodents) and bind to its receptors binding pocket leading to augmentation of responses such as lipogenesis and insulin insensitivity. Glucocorticoids have a lot of important implications in modulating inflammatory responses, metabolism, and in particular, they are known as "classical stress hormones". However, there are no previous studies on TF role as an immunomodulatory agent and is still not clear if TF interfere with corticosterone function as GR agonist or antagonist. Thus, the first objective of the study was to evaluate immunomodulatory aspect of TF by measuring spleen and serum cytokines and the second objective was to measure the level of blood serum corticosterone in TF-exposed male mice using ELISA technique. The results demonstrated that TF-exposed mice have significantly lower serum level of corticosterone compared to controls. The cytokine profile resembles the HPA axis mode with increased levels of Il-4, IL-10, IL-13, and IL-17A whereas the level of IFN-ɣ was decreased. The level of TNF-α (pro-inflammatory cytokine) is significantly higher than controls and it can be explained by many factors, particularly by high level of IL-17A. As a conclusion, TF might act as immunosuppressive agent in experimental animals via the mechanism that resembles the action of glucocorticoids in HPA axis that was as the most reasonable and sufficient model to explain all the found study results in complex.