Figures & data
Notes: Chart showing the circadian rhythm of cortisol production as well as levels of IL-6 in RA patients. The optimal time frame for prednisone application is indicated by the two arrows. Since this nocturnal medication is impractical, the formulation of MR-prednisone with a time-delayed release of the acting agent was developed. Adapted with permission from © 2007 by the American College of Rheumatology. Straub RH, Cutolo M. Circadian rhythms in rheumatoid arthritis: implications for pathophysiology and therapeutic management. Arthritis Rheum. 2007;56(2):399–408.Citation22
Abbreviations: IL-6, interleukin 6; MR, modified-release; RA, rheumatoid arthritis.
Abbreviations: IL-6, interleukin 6; MR, modified-release; RA, rheumatoid arthritis.
Notes: Shown are ingestion, liberation, and way of action of modified-release prednisone in a simplified manner. The coating (1), displayed here in light gray, bursts approximately 4 hours after ingestion due to water penetrationCitation36 and releases the acting prednisone (blue) (2). As a lipophilic hormone, it is able to freely pass the plasma membrane. When reaching the cytosol, it binds (3) to the cytosolic glucocorticoid receptor (cGCR; orange), forming a complex and translocates into the nucleus. Within the nucleus, the complex either binds (4) to glucocorticoid response elements (GREs; yellow) as a dimer which in turn leads to increased production (green) of anti-inflammatory proteins, such as Annexin A1 (right side), or interferes negatively with transcription factors (TF; gray), resulting in a suppression (red) of pro-inflammatory proteins, such as interleukin 6 (IL-6) (left side). The also proposed nongenomic effects are not shown for reasons of clarity and comprehensibility.