Cortisol is a key hormone in the fish stress response with a well-known ability to regulate several physiological functions, including energy metabolism and the immune system. However, data concerning cortisol effects on fish innate immune system using a more controlled increase in cortisol levels isolated from any other stress related signaling is scarce. The present study describes the effect of doses of cortisol corresponding to acute and chronic levels on the complement and lysozyme activity in plasma of the rainbow trout (Oncorhynchus mykiss). We also evaluated the effects of these cortisol levels (from intraperitoneally implanted hydrocortisone) on the mRNA levels quantified by RT-qPCR of selected key immune-related genes in the liver, head kidney, and spleen. For that purpose, 60 specimens of rainbow trout were divided in to two groups: a control group injected with a coconut oil implant and another group injected with the same implant and cortisol (50？μg cortisol/g body weight). Our results demonstrate the role of cortisol as a modulator of the innate immune response without the direct contribution of other stress axes. Our results also show a relationship between the complement and lysozyme activity in plasma and mRNA levels in liver, supporting the important role of this organ in producing these immune system proteins after a rise of cortisol in the fish plasma. 1. Introduction In fish, as in mammals, the innate immune system is the first line of defense against infection that acts by recognizing and attacking nonspecifically the pathogens and helping to maintain homeostasis and health [1–3]. Among its components, some plasma proteins, such as complement components and lysozyme, are of primary importance. These humoral proteins act by lysing bacteria [4, 5] and it has been demonstrated that they are in the core response of fish immunity [6] and that these responses are mediated by cytokines [7, 8]. The response of the innate immune system may be modified by external stimuli, particularly stressors, which most often are known to induce immunosuppressive effects in fish [7, 9, 10]. Thus, it has been shown that stressed fish have decreased activity of complement, hemagglutination, and reduction of circulating lymphocytes [11, 12]. Decreases in C3 complement component protein levels [13] and decrease in expression of immune-relevant genes [14, 15] have also been found. Generally, the immunosuppressive consequences of stressors are attributed to the action of circulating glucocorticoids, in particular cortisol. Both in mammals and fish, cortisol
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