The aquatic environment is massively polluted with endocrine-disrupting compounds (EDCs) including synthetic estrogens (e.g. 17α-ethinylestradiol, EE2) and alkylphenols (e.g. 4-tert-octylphenol, 4t-OP). A major mechanism of action for estrogenic EDCs is their interaction with estrogen receptors and consequently their modulation of the action of enzymes involved in steroid conversion e.g. aromatase CYP19.

We now studied the effects of EE2 and 4t-OP on the anti-bacterial immune response of common carp. We investigated effects on the number/composition of inflammatory leukocytes and on the gene expression of mediators that regulate inflammation and EDC binding. In vitro we found that high concentrations of both EE2 and 4t-OP down-regulated IFN-γ2 and IFN-γ-dependent immune responses in LPS-stimulated monocytes/macrophages. Similarly, during bacterial infection in fish, in vivo treated with EE2 and 4t-OP, decreased gene expression of il-12p35 and of ifn-γ2 was found in the focus of inflammation. Moreover, during A. salmonicida-induced infection in EE2-treated carp, but not in fish fed with 4t-OP-treated food, we found an enhanced inflammatory reaction manifested by high number of inflammatory peritoneal leukocytes, including phagocytes and higher expression of pro-inflammatory mediators (inos, il-1β, cxcl8_l2). Furthermore, in the liver, EE2 down-regulated the expression of acute phase proteins: CRPs and C3. Importantly, both in vitro and in vivo, EDCs altered the expression of estrogen receptors: nuclear (erα and erβ) and membrane (gpr30). EDCs also induced up-regulation of the cyp19b gene.

Our findings reveal that contamination of the aquatic milieu with estrogenic EDCs, may considerably violate the subtle and particular allostatic interactions between the immune response and endogenous estrogens and this may have negative consequences for fish health.

水生环境受到内分泌干扰化合物（EDC）的严重污染，其中包括合成雌激素（例如17α-炔雌醇，EE2）和烷基酚（例如4-叔辛基苯酚，4 t -OP）。雌激素EDC的主要作用机理是它们与雌激素受体的相互作用，因此它们对参与类固醇转化的酶（例如芳香酶CYP19）的作用的调节。

现在，我们研究了EE2和4 t -OP对鲤鱼抗菌免疫反应的影响。我们调查了炎症白细胞的数量/组成以及调节炎症和EDC结合的介体的基因表达的影响。在体外，我们发现在LPS刺激的单核细胞/巨噬细胞中，高浓度的EE2和4 t -OP下调了IFN-γ2和IFN-γ依赖性免疫应答。类似地，在鱼的细菌感染期间，在体内用EE2和4 t -OP处理，发现炎症的焦点是il-12p35和ifn-γ2的基因表达降低。此外，在沙门氏菌诱导的感染在EE2处理的鲤鱼中发生，但在用4 t -OP处理的食物喂养的鱼中未发生，我们发现炎症反应增强，其表现为大量的炎症性腹膜白细胞（包括吞噬细胞）和促炎性介质（inos ，il-1β，cxcl8_l2）。此外，在肝脏中，EE2下调了急性期蛋白：CRP和C3的表达。重要的是，在体外和体内，EDC都会改变雌激素受体的表达：核（erα和erβ）和膜（gpr30）。EDCs也诱导cyp19b基因上调。

我们的发现表明，雌激素EDC对水环境的污染可能会严重破坏免疫反应与内源性雌激素之间的微妙而特殊的异位相互作用，这可能会对鱼类健康产生负面影响。