Impact of Hydrocortisone and of CRH Infusion on the Hypothalamus-Pituitary-Adrenocortical Axis of Septic Male Mice.

PURPOSE: Sepsis is hallmarked by high plasma cortisol/corticosterone (CORT), low adrenocorticotropic hormone (ACTH), and high pro-opiomelanocortin (POMC). While corticotropin-releasing hormone-(CRH) and arginine-vasopressin (AVP)-driven pituitary POMC expression remains active, POMC processing into ACTH becomes impaired. Low ACTH is accompanied by loss of adrenocortical structure, although steroidogenic enzymes remain expressed. We hypothesized that treatment of sepsis with hydrocortisone (HC) aggravates this phenotype whereas CRH infusion safeguards ACTH-driven adrenocortical structure. METHODS: In a fluid-resuscitated, antibiotics-treated mouse model of prolonged sepsis, we compared the effects of HC and CRH infusion with placebo on plasma ACTH, POMC, and CORT; on markers of hypothalamic CRH and AVP signaling and pituitary POMC processing; and on the adrenocortical structure and markers of steroidogenesis. In adrenal explants, we studied the steroidogenic capacity of POMC. RESULTS: During sepsis, HC further suppressed plasma ACTH, but not POMC, predominantly by suppressing sepsis-activated CRH/AVP-signaling pathways. In contrast, in CRH-treated sepsis, plasma ACTH was normalized following restoration of pituitary POMC processing. The sepsis-induced rise in markers of adrenocortical steroidogenesis was unaltered by CRH and suppressed partially by HC, which also increased adrenal markers of inflammation. Ex vivo stimulation of adrenal explants with POMC increased CORT as effectively as an equimolar dose of ACTH. CONCLUSIONS: Treatment of sepsis with HC impaired integrity and function of the hypothalamic-pituitary-adrenal axis at the level of the pituitary and the adrenal cortex while CRH restored pituitary POMC processing without affecting the adrenal cortex. Sepsis-induced high-circulating POMC may be responsible for ongoing adrenocortical steroidogenesis despite low ACTH.

Black Turmeric and Aloe Vera in the Management of Oral Submucous Fibrosis: A Prospective Clinical Study.

AIM: To determine the therapeutic efficacy of Kali haldi in the management of Oral submucous Fibrosis (OSMF) v/s steroid therapy. MATERIALS AND METHODS: A clinical prospective study was conducted on 42 patients of oral submucous fibrosis were equally divided into 2 groups. Group A patients were treated with a mixture of powdered Kali Haldi and aloe vera gel in equal ratio 3 times a day for 3 months. Group B patients were treated with intralesional injection of hydrocortisone and hyaluronidase for 6 weeks with oral antioxidant supplements for 3 months. Burning sensation, cheek flexibility, mouth opening, and tongue protrusion were evaluated before, during, and after treatment at an interval of 15 days, 1 month, 2, month and 3 months. RESULTS: Statistically significant results were obtained at the end of 3 months duration for both the groups (P < 0.001). The Symptomatic correction was more evident in the case of Group A patients than Group B. Response of the ayurvedic regimen was potentially better as compared to the regular steroid therapy. CONCLUSION: The study concludes that Combination therapy works wonders in the case of OSMF in stages I, II, III and can be a good option, comparatively safe and with negligible side effects, but potent and equally effective management of oral submucous fibrosis. Henceforth, it will be better to do such kinds of studies on a vast scale including larger samples and longer duration to check the efficacy and durability of this ancient ayurvedic regimen.

Treatment of subcutaneous nodules after infusion of apomorphine; a biopsy-controlled study comparing 4 frequently used therapies.

This study aimed to provide clinical evidence for existing treatments of subcutaneous nodules after subcutaneous infusion of apomorphine, using a biopsy-controlled prospective crossover design of four treatments. We demonstrated that dilution of apomorphine significantly improved patient satisfaction, while subcutaneous hydrocortisone reduced nodule size, however with no differences in the histopathology.

Efficacy and safety of Soshiho-tang in atopic dermatitis patients with gastrointestinal disorders: A double-blinded, randomized, and placebo-controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Because of the growing incidence of AD, psychosocial and economic burden of AD patients are often considerable. Steroid treatments are widely used, but long term use of this treatment can cause side effects. To reduce the burden of AD patients and find new efficient treatment, this study chose Soshiho-tang, a traditional medicine used in eastern Asia. AIM OF THE STUDY: Soshiho-tang (SSHT) is a traditional herbal medicine that has anti-inflammatory effects and improves immune function. This clinical trial evaluated the efficacy and safety of SSHT in atopic dermatitis (AD) patients with gastrointestinal disorders in comparison with placebo. MATERIALS AND METHODS: This study was a single-center, randomized, double-blinded, placebo-controlled, and investigator-initiated clinical trial. A total of 60 patients aged 3-18 years with gastrointestinal disorders and diagnosed with AD by Hanifin & Rajka criteria with a Scoring Atopic Dermatitis (SCORAD) index between 15 and 49 were enrolled. Participants were randomly assigned to the SSHT or placebo groups in a ratio of 1:1 and efficacy evaluation was conducted at week 4 and 8. The participants orally administered SSHT or placebo three times a day for 4 weeks. The primary outcome was measured based on a change of SCORAD index. The secondary outcome measurements included the following: survey questionnaires of gastrointestinal disorder, amount and frequency of ointment application for AD, dermatology quality of life index, and safety evaluation (diagnostic test, adverse reaction, and vital sign monitoring). RESULTS: During efficacy evaluation, the SCORAD score and digestive symptoms in the experimental and placebo groups were not statistically significant. However, the amount and frequency of ointment application in the experimental group were reduced compared to those in the placebo group at week 8. Also, In the Children's Dermatology Life Quality Index (CDLQI), statistically significant Quality of Life (QOL) improvement was observed in the SSHT experimental group compared to the placebo group. In safety evaluation, all participants were within the normal range during the study period. Blood sample testing indicated that the lymphocytes ratio decreased, and neutrophils ratio increased in the experimental group, whereas the placebo group showed the opposite immune response pattern. CONCLUSION: We concluded that SSHT administration can reduce steroid ointment dependence and improve the QOL in AD patients by regulating neutrophil-lymphocyte ratio.

Y-site physical compatibility of hydrocortisone continuous infusions with admixtures used in critically ill patients.

PURPOSE: Critically ill patients with septic shock often receive multiple intravenous medications, necessitating either the placement of separate lines for medication administration or administration of medications concurrently through a Y-site connector only where compatibility has been demonstrated. The purpose of this study was to examine the physical compatibility of hydrocortisone infusions and select intravenous medications through a simulated Y site. METHODS: The medications tested for simulated Y-site physical compatibility with hydrocortisone included acetaminophen, albumin, cefepime, ciprofloxacin, cisatracurium, doripenem, epinephrine, esomeprazole, ibuprofen, levofloxacin, levothyroxine, meropenem, and norepinephrine. Hydrocortisone in solution with 0.9% sodium chloride injection was combined with an equivalent volume of solutions of each test drug at maximum or commercially available concentrations used clinically in intensive care units, as appropriate. The samples were evaluated using turbidimetric measurements and examined visually against light and dark backgrounds to determine physical compatibility. Observations and analyses were completed over a one-hour period at 15-minute intervals beginning immediately after mixing. Each test was performed in triplicate. RESULTS: All study medications demonstrated visual and/or turbidimetric physical compatibility when combined with hydrocortisone in a simulated Y-site infusion. No medications demonstrated a visual physical incompatibility when combined with hydrocortisone. CONCLUSION: Acetaminophen, albumin, cefepime, ciprofloxacin, cisatracurium, doripenem, epinephrine, esomeprazole, ibuprofen, levofloxacin, levothyroxine, meropenem, and norepinephrine exhibited physical compatibility with hydrocortisone via Y-site infusion.

Intravenous Infusion of Cortisol, Adrenaline, or Noradrenaline Alters Porcine Immune Cell Numbers and Promotes Innate over Adaptive Immune Functionality.

Despite the importance of pigs (Sus scrofa domestica) in livestock production and their increasing role as a model organism for human physiology, knowledge about the porcine immune system under the influence of stress hormones is fragmentary. Exceptionally little is known about the effects of catecholamines. Therefore, the aim of this study was to examine the in vivo effects of adrenaline, noradrenaline, and cortisol on number and functionality of porcine blood immune cells. Castrated male pigs (n = 34) were treated with physiological doses of either adrenaline, noradrenaline, or cortisol via i.v. infusion for 48 h. Blood samples were collected before treatment (-24 h, -22 h, 0 h), during treatment (+2 h, +24 h, +48 h), and at 72 h postinfusion. Immune cell numbers and phagocytic activity were evaluated by flow cytometry and lymphocyte proliferation by 3H-thymidine incorporation. Total IgG and IgM Ab levels were determined via ELISA. Pigs receiving cortisol showed strongly decreased adaptive immune cell numbers and increased neutrophils, accompanied by hampered lymphocyte proliferation but increased monocyte phagocytosis. Catecholamine effects on immune cell numbers were mostly similar to cortisol in direction but smaller in intensity and duration. Lymphocyte proliferation was inhibited after 2 h of noradrenaline infusion, and both catecholamines promoted monocyte and neutrophil phagocytosis. These findings indicate a shift from adaptive to innate immunity in stressful situations. This study is the first (to our knowledge) to systematically investigate specific glucocorticoid and catecholamine actions on the porcine immune system in this level of detail and confirms many similarities to humans, thus strengthening the pig as a human model in psychoneuroimmunology.

Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency in a Tunisian family.

Congenital adrenal hyperplasia refers to a group of rare genetic disorders affecting the adrenal glands. 21-hydroxylase deficiency is the most prevalent and the most studied cause while the remaining enzymatic defects are less common, accounting for less than 10% of cases. We herein described the clinical, biological and molecular characteristics and outcome of patients of the same family diagnosed with 11-Beta-hydroxylase deficiency. The disorder was revealed by peripheral precocious puberty between the age of 2-3 years in males and by the virilization of the external genitalia in females. Genetics finding a homozygous p.Gly379Val mutation in the CYP11B1 gene. All patients received hydrocortisone supplementation therapy and mineralocorticoid-receptor antagonist. The females underwent a surgical correction of the ambiguous genitalia at the neonatal age. Long term follow-up revealed metabolic syndrome, obesity and hypertension in the first two patients, an impaired final height in the two females and hypokalemia in three patients.

Acute adrenal failure: a potentially fatal consequence of an adulterated herbal remedy.

Herbal remedies adulterated with glucocorticoids can cause Cushing's syndrome. We report a severe presentation of a 'herbal remedy' adulterated with glucocorticoids; causing a potentially fatal adrenal crisis precipitated by acute illness. Investigations were consistent with adrenal suppression and confirmed, after tablet analysis, to be due to a 'herbal remedy' containing synthetic betamethasone/dexamethasone. This case highlights the need for clinical vigilance and patient education about the potential risks associated with the use of unlicensed treatments and the role of tablet analysis in routine biochemistry.

[Optimization of reparative dentinogenesis in experimental osteoporosis]. / Optimizatsiia reparativnogo dentinogeneza pri éksperimental'nom osteoporoze.

The aim of the study was to assess histochemical changes of the dental pulp in direct pulp capping/experimental osteoporosis animal model. The study was performed on 20 two-year sheep with simulated acute pulpitis divided in 2 groups: main (15 animals/120 teeth) and control (5 animals/40 teeth). Direct pulp capping in the main group included tissue-engineered structure composed of a hydrogel PuraMatrix/3DM with ectomesenchymal stem cells immobilized on collagen sponge. In the control group collagen sponges with hydrocortisone furatsilin, chondroitin sulfate, аnaesthesinum were used for the same purpose. Dentinal bridge formation was much slower in controls than in the main group. Developed tissue-engineered design optimizes each stage of the healing process by protecting the pulp from infection, reduction of exudation, hemostatic effect and in long term contributes to a significant acceleration of the formation of the dentinal bridge.

Diagnosis and management of idiopathic facial palsy in children.

Idiopathic or Bell's palsy is an acute peripheral-nerve palsy involving the facial nerve. The disorder is quite infrequent under the age of 10 years. The proposed etiologies of Bell's palsy include ischemic neuropathy and vascular diseases. This case series presents five children with Bell's palsy. The epidemiologic, diagnostic and therapeutic measures were summarized. The evolution regarding especially the facial motricity was detailed. The results about the role of some thrombophilic polymorphisms suggest a probable involvement of factor V haplotype, MTHFR and factor XIII in the etiology of Bell's palsy in five Tunisian children.

[Addison's disease : Primary adrenal insufficiency]. / Morbus Addison : Primäre Nebenniereninsuffizienz.

Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease. Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH. Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises. Patients with adrenal insufficiency should carry an emergency card and emergency kit with them.

Effects of anesthesia with the essential oil of Ocimum gratissimum L. in parameters of fish stress / Efeitos da anestesia com o óleo essencial de Ocimum gratissimum L. em parâmetros de estresse de peixes

RESUMO: The effects of anesthesia with the essential oil of Ocimum gratissimum (EOO) in parameters of stress after handling were investigated in silver catfish (Rhamdia quelen). EOO was obtained from the aerial parts by hydrodistillation. Juveniles were anesthetized with 70 or 300 mg L-1 EOO and submitted to air exposure for 1 minute. The fishes were sampled immediately or transferred to anesthetic-free aquaria until sampling. In the first experiment, juveniles had their blood collected at 0, 1, 4, and 8 h after handling to assay plasma cortisol and blood glucose levels. The unanesthetized animals were restrained manually for blood collection. In the second experiment, water samples of the recovery aquaria were collected to evaluate net ion fluxes at 0 - 4 h and 4 - 8 h. Water and ethanol controls were also performed under the same conditions. The results showed that the cortisol levels did not differ among the treatments. Hyperglycemia was verified in fish exposed to 70 and 300 mg L-1 EOO at 1 h and 4 h after handling. After 8 h, cortisol and glucose concentrations were lower or similar than those from immediately after handling for all treatments. EOO anesthesia prevented Na+ efflux observed in the control groups in both flux periods. There were net Cl- and K+ effluxes at 0 - 4 h and influxes at 4 - 8 h after handling in most treatments, and these fluxes did not differ among the treatments. The results suggest that EOO did not impair stress recovery and did not act as an additional handling stressor in silver catfish.

RESUMO: Os efeitos da anestesia com o óleo essencial de Ocimum gratissimum (EOO) em parâmetros de estresse após manuseio foram investigados em jundiás (Rhamdia quelen). EOO foi obtido a partir das partes aéreas por hidrodestilação. Os juvenis foram anestesiados com 70 ou 300 mg L-1 de EOO e expostos ao ar por 1 minuto. Os peixes foram amostrados imediatamente ou transferidos para aquários sem anestésico até amostragem. No primeiro experimento, os juvenis tiveram seu sangue coletado em 0, 1, 4, e 8 h após manuseio para avaliar os níveis de cortisol e glicemia. Os animais não anestesiados foram contidos manualmente para coleta sanguínea. No segundo experimento, amostras de água foram coletadas do aquário de recuperação dos animais para avaliação do fluxo iônico entre 0 - 4 h e 4 - 8 h. Grupos controles em água e etanol também foram realizados sobre as mesmas condições. Os resultados demonstraram que os níveis de cortisol não diferiram entre os tratamentos. Hiperglicemia foi detectada em peixes expostos a 70 e 300 mg L-1 de EOO em 1 h e 4 h após o manuseio. Após 8 h, os teores de cortisol e glicose foram menores ou similares aqueles imediatamente após o manuseio para todos os tratamentos. A anestesia com EOO preveniu o efluxo de Na+ observado para os grupos controle em ambos os períodos avaliados. Ocorreram efluxos de Cl- and K+ entre 0 - 4 h e influxos entre 4 - 8 h após o manuseio para a maioria dos tratamentos, e estes eventos não diferiram entre os tratamentos. Os resultados sugerem que o EOO não prejudica a recuperação do animal frente ao evento estressor ou atua como estressor adicional ao manuseio em jundiás.

Steroid-induced hypocalcaemia with tetany in a patient with hypoparathyroidism.

Although glucocorticoids have a known negative effect on calcium balance, they do not normally cause clinically significant hypocalcaemia. A young woman with post-surgical hypoparathyroidism developed symptomatic hypocalcaemia on two occasions following treatment with intravenous hydrocortisone for allergic reactions. Oral calcium and vitamin D supplementation could not prevent the development of hypocalcaemia. She was treated successfully with intravenous calcium gluconate infusions and discontinuation of glucocorticoids. In patients with hypoparathyroidism, impaired parathyroid hormone response to steroid-induced negative calcium balance may result in severe symptomatic hypocalcaemia requiring hospitalisation.

Comparative study between Ephedra sinica Stapf and Fructus Schisandrae Chinensis on ET-1 and 6-keto-prostaglandin F1α in rats with idiopathic pulmonary fibrosis.

The aim of this study was to evaluate differences in the effects of Ephedra sinica Stapf and Fructus Schisandrae Chinensis on angiogenesis in the treatment of bleomycin-induced rat idiopathic pulmonary fibrosis. The rat models were created using bleomycin. The animals were divided into six groups: model, control, Ephedra alone, Schisandrae alone, combination of Ephedra and Schisandrae, and hydrocortisone alone. The treatments were administered for 28 days. After 7 and 28 days, the rats were sacrificed for pathological morphology examination, microvascular density determination, and angiogenesis-related cytokine examination. The Ephedra and hydrocortisone groups demonstrated significantly reduced alveolitis and pulmonary fibrosis grades compared with the model group (P < 0.05). The number of blood vessels in the Ephedra group was higher than that in the Schisandrae and combination therapy groups. At 7 days, the expression level of endothelin (ET)-1 in the model group was significantly higher than that in the normal group (P < 0.01). The level of 6-keto-prostaglandin F1α (6-keto-PGF1α) in the treatment group increased, and there were significant differences between the Ephedra group and the combination therapy and normal groups (P < 0.05). Ephedra inhibited the increase in the lung coefficient. The combination therapy prevented pulmonary artery injury and angiogenesis of the arteries by reducing the level of ET-1 and promoting the level of 6-keto-PGF1α in the blood. Ephedra and Schisandrae prevented alveolitis and the development of pulmonary fibrosis.

Cortisol administration increases hippocampal activation to infant crying in males depending on childhood neglect.

Animal studies show that exposure to parental neglect alters stress regulation and can lead to neural hyposensitivity or hypersensitivity in response to cortisol, most pronounced in the hippocampus. Cortisol, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, has also been related to parenting more directly, for example, in both sexes, cortisol levels increase when listening to infants crying, possibly to activate and facilitate effective care behavior. Severe trauma is known to negatively affect the HPA-axis in humans; however, it is unknown whether normal variation in parental care in the healthy population can alter sensitivity of the hippocampus to cortisol. Here, we investigate whether variation in experienced neglect changes neural sensitivity to cortisol when humans listen to infant crying, which is an unequivocal signal relevant for care behavior. In a placebo-controlled, within-subject neuroimaging study, we administered 40 mg cortisol to 21 healthy young males without children and used a validated task for measuring neural responses to infant crying. The Dutch version of the Childhood Trauma Questionnaire was used to index participants' early exposure to abuse and neglect. The data show that cortisol markedly increased hippocampal activation toward crying infants, and this effect varied significantly with parental neglect, even in our nonclinical subject sample. Without exposure to severe trauma or neglect, reduced self-experienced quality of parental care in the normal range already substantially increased hippocampal responsivity to cortisol. Altered hippocampal sensitivity to cortisol might be a cross-species marker for the risk of developing later life psychopathology.

Combination of fractional erbium-glass laser and topical therapy in melasma resistant to triple-combination cream.

BACKGROUND: Melasma is a common melanosis often difficult to treat. OBJECTIVE: The aim of this paper was to report on the safety and efficacy of non-ablative fractional photothermolysis combined with the use of triple-combination cream (TCC) on a large population with melasma resistant (i.e., with no complete/near-complete clearing) to TCC alone. METHODS: Seventy-six patients with resistant melasma underwent a combined treatment protocol. The protocol consisted of a TCC (hydroquinone 4%, retinoic acid 0.03%, hydrocortisone butyrate 0.1%) applied daily for 10 days followed by four laser treatments performed in 3-week intervals with a fractional 1540-nm erbium-glass laser. During these intervals, and for 3 months after the last laser session, TCC was also applied daily following a "pulse-therapy" scheme. Improvement was assessed by the melasma-area-and-severity-index (MASI) score. RESULTS: At 1 month, marked (>75%) and moderate (51-75%) clearing of melasma were observed in 46 of 76 (67.1%) and 12 of 76 (21%) cases, respectively. At 6 months, we noticed a marked improvement in 16 of 76 (21.1%) and no improvement in 33 of 76 (43.4%) patients. CONCLUSION: Our study proposes the combination of NFP/TCC as a useful therapy for patients with melasma resistant to TCC alone, but it shows that its long-term efficacy is limited.

Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats.

INTRODUCTION: The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. METHODS: Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. RESULTS: We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood-brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. CONCLUSIONS: Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus.

First evidence of the possible implication of the 11-deoxycorticosterone (DOC) in immune activity of Eurasian perch (Perca fluviatilis, L.): comparison with cortisol.

Cortisol, the main corticosteroid in fish, is frequently described as a modulator of fish immune system. Moreover, 11-deoxycorticosterone (DOC) was shown to bind and transcriptionally activate the mineralocorticoid receptor and may act as a mineralocorticoid in fish. Immune modulations induced by intraperitoneal injections of these two corticosteroids were assessed in Eurasian perch juveniles. Cortisol and DOC were injected at 0.8 mg kg(-1) and 0.08 mg kg(-1) body weight respectively. Cortisol increased plasma lysozyme activity 72 h post-injection, C-type lysozyme expression in spleen from 1 to 72 h post-injection, and favoured blood neutrophils at the expense of a mixture of lymphocytes and thrombocytes. Moreover, 6 h after injection, cortisol reduced expression levels of the pro-inflammatory cytokine TNF-α in spleen. DOC had no effects on the immune variables measured in plasma, but increased expression levels of C-type lysozyme and apolipoprotein A1 mRNA in both gills and spleen. Meanwhile, DOC stimulated its putative signalling pathway by increasing expression of mineralocorticoid receptor and 11ß-hydroxysteroid dehydrogenase-2 in spleen. These results confirmed the role of cortisol as an innate, short term immune stimulator. For the first time, DOC is described as a possible immune stimulator in fish.