Dexamethasone is a glucocorticoid receptor agonist and an IL receptor modulator.Dexamethasone inhibits production of exosomes containing inflammatory microRNA-155 in lipopolysaccharide-induced macrophage inflammatory responses
GM-CSF release from A549 cells was inhibited by dexamethasone (EC50 = 2.2 nM). The concentration-dependent ability of dexamethasone (EC50 = 36 nM) to induce transcription of the beta2-receptor was found to correlate with GR DNA binding and occurred at 10-100 fold higher concentrations than the inhibition of GM-CSF release . Following treatment with 1 microM dexamethasone, there was a decrease in transmonolayer paracellular permeability mainly to sucrose, fluorescein, and dextrans of up to 20 KDa .
Kd values (mean+/-SE) for cortisol in human mononuclear leukocytes (HML) of hypertensive patients were higher than in control subjects (24.6 versus 17.5 nmol/L). Binding capacity (4978 versus 4131 sites/cell), Kd values for dexamethasone (6.7 versus 5.7 nmol/L), and IC50 values for dexamethasone (3.4 versus 3.1 nmol/L) and cortisol (12.2 versus 9.5 nmol/L) were not significantly different . Powerful reduction of neutrophils in bronchoalveolar lavage fluid (BALF) was obtained by a single i.p. injection of dexamethasone (10 mg/kg), whereas treatment with N-acetylcysteine (NAC) only resulted in reduction of neutrophils when administered at a high dose (500 mg/kg). A significant decrease of tumour necrosis factor-alpha, IL-1alpha, IL-1beta IL-6, IL- 12p40, and MIP-1alpha mRNA when mice where treated with dexamethasone but not when treated with NAC .
NAC was administered at three different doses (10, 100 and 500 mg/kg body weight). At the highest concentration, the acidic pH of the NAC solution was adjusted by adding NaOH. Dexamethasone was administered as a single injection of 1 or 10 mg/kg. Both drugs were dissolved in saline and 400 μl were injected intraperitoneally, either 1 h before or 1 h after LPS exposure. In one experiment, NAC (100 and 500 mg/kg) was injected successively every 4·5 h, starting 1 h before challenge (five injections in total). A control group of LPS-exposed animals were injected intraperitoneally with solvent alone (saline). Intratracheal administration was performed by instillation of 100 μl NAC (50, 100 or 500 mg/kg) or dexamethasone (10 mg/kg) into the lungs of mice anaesthetized with 15 mg/kg Rapinovet (i.v.) .