Inflammation is the evolutionary conserved immune response to harmful stimuli such as pathogens or damaged cells. This multistep process acts by removing injurious stimuli and initiating the healing process. Therefore, it must be tightly regulated by cytokines, chemokines, and enzymes, as well as neuroendocrine mediators. In the present work, we studied the immunoregulatory properties of 17β-estradiol (E2) in common carp. We determined the in vitro effects of E2 on the activity/polarization of macrophages and the in vivo effects during Aeromonas salmonicida-induced inflammation. In vitro, E2 reduced the lipopolysaccharide (LPS)-stimulated expression of pro- and anti-inflammatory mediator genes but did not change the gene expression of the estrogen receptors and of aromatase CYP19. In contrast, in vivo in the head kidney of A. salmonicida-infected fish, E2-treated feeding induced an upregulation of gene expression of pro-inflammatory (il-12p35 and cxcb2) and anti-inflammatory (arginase 1, arginase 2, il-10, and mmp9) mediators. Moreover, in infected fish fed with E2-treated food, a higher gene expression of the estrogen receptors and of the aromatase CYP19 was found. Our results demonstrate that estrogens can modulate the carp innate immune response, though the in vitro and in vivo effects of this hormone are contrasting. This implies that estradiol not only induces a direct effect on macrophages but rather exerts immunomodulatory actions through indirect mechanisms involving other cellular targets.

炎症是对有害刺激物（如病原体或受损细胞）的进化保守免疫反应。该多步骤过程通过消除有害刺激并启动愈合过程来起作用。因此，它必须受到细胞因子，趋化因子和酶以及神经内分泌介质的严格调节。在目前的工作中，我们研究了鲤鱼中17β-雌二醇（E2）的免疫调节特性。我们确定了E2对巨噬细胞活性/极化的体外作用以及鲑鱼气单胞菌的体内作用引起的炎症。在体外，E2降低了脂多糖（LPS）刺激的促炎和抗炎介质基因的表达，但未改变雌激素受体和芳香酶CYP19的基因表达。相反，在体内，在经沙门氏菌感染的鱼的头部肾脏中，经E2处理的喂养诱导了促炎性基因（il-12p35和cxcb2）和抗炎性基因（精氨酸酶1，精氨酸酶2，il）的基因表达上调。-10和mmp9）调解员。此外，在喂食经E2处理的食物的受感染鱼中，发现雌激素受体和芳香化酶CYP19的基因表达更高。我们的结果表明，雌激素可以调节鲤鱼固有的免疫反应，尽管这种激素的体外和体内作用是相反的。这意味着雌二醇不仅诱导对巨噬细胞的直接作用，而且通过涉及其他细胞靶标的间接机制发挥免疫调节作用。