Hydrocortisone

Hydrocortisone is a main glucocorticoid secreted by the adrenal cortex.

Hydrocortisone and triiodothyronine regulate hyaluronate synthesis in a tissue-engineered human dermal equivalent through independent pathways.[Pubmed:25277518]

J Biosci Bioeng. 2015 Feb;119(2):226-36.

Hydrocortisone (HC) and triiodothyronine (T3) have both been shown to be capable of independently inhibiting hyaluronate (HA, hyaluronic acid) synthesis in a self-assembled human dermal equivalent (human dermal matrix). We sought to investigate the action of these two hormones in concert on extracellular matrix formation and HA inhibition in the tissue engineered human dermal matrix. To this end, neonatal human dermal fibroblasts were cultured in defined serum-free medium for 21 days in the presence of each hormone alone, or in combination, in varying concentrations. Through a process of self-assembly, a substantial dermal extracellular matrix formed that was characterized. The results of these studies demonstrate that combinations of the hormones T3 and Hydrocortisone showed significantly higher levels of hyaluronate inhibition as compared to each hormone alone in the human dermal matrix. In order to gain preliminary insight into the genes regulating HA synthesis in this system, a differential gene array analysis was conducted in which the construct prepared in the presence of 200 mug/mL HC and 0.2 nM T3 was compared to the normal construct (0.4 mug/mL HC and 20 pM T3). Using a GLYCOv4 gene chip containing approximately 1260 human genes, we observed differential expression of 131 genes. These data suggest that when these two hormones are used in concert a different mechanism of inhibition prevails and a combination of degradation and inhibition of HA synthesis may be responsible for HA regulation in the human dermal matrix.

Hydrocortisone prevents immunosuppression by interleukin-10+ natural killer cells after trauma-hemorrhage.[Pubmed:25289930]

Crit Care Med. 2014 Dec;42(12):e752-61.

OBJECTIVE: Trauma induces a state of immunosuppression, which is responsible for the development of nosocomial infections. Hydrocortisone reduces the rate of pneumonia in patients with trauma. Because alterations of dendritic cells and natural killer cells play a central role in trauma-induced immunosuppression, we investigated whether Hydrocortisone modulates the dendritic cell/natural killer cell cross talk in the context of posttraumatic pneumonia. DESIGN: Experimental study. SETTINGS: Research laboratory from an university hospital. SUBJECTS: Bagg Albino/cJ mice (weight, 20-24 g). INTERVENTIONS: First, in an a priori substudy of a multicenter, randomized, double-blind, placebo-controlled trial of Hydrocortisone (200 mg/d for 7 d) in patients with severe trauma, we have measured the blood levels of five cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-10, interleukin-12, interleukin-17) at day 1 and day 8. In a second step, the effects of Hydrocortisone on dendritic cell/natural killer cell cross talk were studied in a mouse model of posttraumatic pneumonia. Hydrocortisone (0.6 mg/mice i.p.) was administered immediately after hemorrhage. Twenty-four hours later, the mice were challenged with Staphylococcus aureus (7 x 10 colony-forming units). MEASUREMENTS AND MAIN RESULTS: Using sera collected during a multicenter study in patients with trauma, we found that Hydrocortisone decreased the blood level of interleukin-10, a cytokine centrally involved in the regulation of dendritic cell/natural killer cell cluster. In a mouse model of trauma-hemorrhage-induced immunosuppression, splenic natural killer cells induced an interleukin-10-dependent elimination of splenic dendritic cell. Hydrocortisone treatment reduced this suppressive function of natural killer cells and increased survival of mice with posthemorrhage pneumonia. The reduction of the interleukin-10 level in natural killer cells by Hydrocortisone was partially dependent on the up-regulation of glucocorticoid-induced tumor necrosis factor receptor-ligand (TNFsf18) on dendritic cell. CONCLUSIONS: These data demonstrate that trauma-induced immunosuppression is characterized by an interleukin-10-dependent elimination of dendritic cell by natural killer cells and that Hydrocortisone improves outcome by limiting this immunosuppressive feedback loop.

The effects of chronic administration of hydrocortisone on cognitive function in normal male volunteers.[Pubmed:10494574]

Psychopharmacology (Berl). 1999 Aug;145(3):260-6.

RATIONALE: Corticosteroids are elevated in certain neuropsychiatric disorders and this may contribute to the neuropsychological impairments reported in these disorders. OBJECTIVE: To examine the effects of Hydrocortisone on learning, memory and executive function. METHODS: Hydrocortisone 20 mg was administered twice daily for 10 days to normal male volunteers in a randomized, placebo control, crossover, within-subject design. Learning, memory and executive function were measured using selected subtests from the Cambridge Neuropsychological Test Automated Battery. RESULTS: Hydrocortisone caused impairments of visuo-spatial memory. These included increased within search errors and impaired use of strategies on the spatial working memory subtest. In addition, administration of Hydrocortisone was associated with more errors in the paired associate learning subtest, although no effect was found on the Tower of London. Hydrocortisone speeded response latencies in certain tests (pattern and spatial recognition memory). CONCLUSION: These results indicate that chronic administration of Hydrocortisone leads to deficits in certain tests of cognitive function sensitive to frontal lobe dysfunction and may contribute to the cognitive impairment reported in certain neuropsychiatric disorders.

Hydrocortisone suppresses intranuclear activator-protein-1 (AP-1) binding activity in mononuclear cells and plasma matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9).[Pubmed:11739475]

J Clin Endocrinol Metab. 2001 Dec;86(12):5988-91.

Having demonstrated recently that Hydrocortisone (HC) suppresses intranuclear and total cellular nuclear factor-kappa B (NF-kappa B) and increases inhibitor kappa B (I kappa B) in mononuclear cells (MNC), in vivo, we have now investigated the effect of Hydrocortisone on the other major pro-inflammatory transcription factor, AP-1 and the two proteins, MMP-2 and MMP-9, whose transcription is modulated by it. MMP's hydrolyze extracellular matrix proteins and thus, allow the spread of inflammation. HC (100 mg) was given intravenously to eight normal subjects following an overnight fast. Blood samples were obtained at 0, 1, 2, 4, 8 and 24 h. MNC were separated and the nuclear fractions and cellular homogenates were prepared by standard techniques. AP-1 binding activity was measured by electrophoretic mobility shift assay (EMSA). Plasma MMP-2 and MMP-9 were measured by ELISA. AP-1 binding activity fell significantly at 1, 2, 4 and 8 h. Plasma MMP-2 concentration also decreased significantly at 1, 2, 4 and 8 h while MMP-9 decreased at 1 and 2 h. These data demonstrate that the acute anti-inflammatory effect of HC, in vivo, is, in part, due to AP-1 suppression and a reduction in MMP-2 and MMP-9. Thus, HC may reduce the extracellular spread of inflammation through the inhibition of matrix metalloproteinases.

Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study.[Pubmed:12426230]

Am J Respir Crit Care Med. 2003 Feb 15;167(4):512-20.

Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of Hydrocortisone therapy. To evaluate the effects of Hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crossover study to receive either the first 100 mg of Hydrocortisone as a loading dose and 10 mg per hour until Day 3 (n = 20) or placebo (n = 20), followed by the opposite medication until Day 6. Hydrocortisone infusion induced an increase of mean arterial pressure, systemic vascular resistance, and a decline of heart rate, cardiac index, and norepinephrine requirement. A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support. The inflammatory response (interleukin-6 and interleukin-8), endothelial (soluble E-selectin) and neutrophil activation (expression of CD11b, CD64), and antiinflammatory response (soluble tumor necrosis factor receptors I and II and interleukin-10) were attenuated. In peripheral blood monocytes, human leukocyte antigen-DR expression was only slightly depressed, whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased. Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects. In conclusion, Hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression.

Cortisol increases gluconeogenesis in humans: its role in the metabolic syndrome.[Pubmed:11724664]

Clin Sci (Lond). 2001 Dec;101(6):739-47.

Android obesity is associated with increased cortisol secretion. Direct effects of cortisol on gluconeogenesis and other parameters of insulin resistance were determined in normal subjects. Gluconeogenesis was determined using the reciprocal pool model of Haymond and Sunehag (HS method), and by the Cori cycle/lactate dilution method of Tayek and Katz (TK method). Glucose production (GP) and gluconeogenesis were measured after a 3 h baseline infusion and after a 4-8 h pituitary-pancreatic infusion of somatostatin, replacement insulin, growth hormone (GH), glucagon and a high dose of cortisol (Hydrocortisone). The pituitary-pancreatic infusion maintains insulin, GH and glucagon concentrations within the fasting range, while increasing the concentration of only one hormone, cortisol. Two groups of five subjects were each given high-dose cortisol administration, and results were compared with those from a group of six 'fasting alone' subjects (no infusion) at 16 and 20 h of fasting. Fasting GP (12 h fasting) was similar in all groups, averaging 12.5+/-0.2 micromol x min(-1) x kg(-1). Gluconeogenesis, as a percentage of GP, was 35+/-2% using the HS method and 40+/-2% using the TK method. After 16 h of fasting, GP had fallen (11.5+/-0.6 micromol x min(-1) x kg(-1)) and gluconeogenesis had increased (55+/-5% and 57+/-5% of GP by the HS and TK methods respectively; P<0.05). High-dose cortisol infusion for 4 h increased serum cortisol (660+/-30 nmol/l; P<0.05), blood glucose (7.9+/-0.5 mmol/l; P<0.05) and GP (14.8+/-0.8 micromol x min(-1) x kg(-1); P<0.05). The increase in GP was due entirely to an increase in gluconeogenesis, determined by either the HS or the TK method (66+/-6% and 65+/-5% of GP respectively; P<0.05). Thus cortisol administration in humans increases GP by stimulating gluconeogenesis. Smaller increases in serum cortisol may contribute to the abnormal glucose metabolism known to occur in the metabolic syndrome.