how does cortisone reduce inflammation

Glucocorticoid Mechanism of Action in Inflammation

Pharmacological Properties of Glucocorticoids

Glucocorticoids, a class of steroid hormones including cortisol and its synthetic analogs such as prednisone and dexamethasone, exert potent anti-inflammatory effects. Their mechanism of action is complex and involves multiple pathways impacting gene transcription and protein synthesis.

Nuclear Receptor Binding and Gene Transcription

Glucocorticoids bind to intracellular glucocorticoid receptors (GRs), which are members of the nuclear receptor superfamily. Upon ligand binding, the GR undergoes a conformational change, translocates to the nucleus, and binds to specific DNA sequences known as glucocorticoid response elements (GREs). This binding either activates or represses the transcription of numerous target genes, leading to widespread effects on cellular processes.

Transcriptional Regulation of Inflammatory Mediators

  • Inhibition of pro-inflammatory cytokine production: Glucocorticoids suppress the transcription of genes encoding pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, thereby reducing the inflammatory cascade.
  • Induction of anti-inflammatory mediators: They stimulate the expression of anti-inflammatory proteins like annexin A1 and lipocortin-1, which further counteract inflammation.
  • Suppression of cyclooxygenase-2 (COX-2): Glucocorticoids reduce the production of COX-2, an enzyme involved in prostaglandin synthesis, thus decreasing the production of these potent inflammatory mediators.
  • Inhibition of phospholipase A2 (PLA2): By suppressing PLA2 activity, glucocorticoids decrease the production of arachidonic acid, a precursor to inflammatory eicosanoids.

Non-Genomic Effects

Beyond their genomic effects, glucocorticoids also exert rapid, non-genomic actions that contribute to their anti-inflammatory properties. These actions may involve direct interactions with membrane-bound receptors or modulation of intracellular signaling pathways, leading to rapid changes in cellular function.

Clinical Implications and Side Effects

Glucocorticoids are widely used to treat various inflammatory conditions, but their prolonged use is associated with significant side effects, including immunosuppression, hyperglycemia, and osteoporosis. Therefore, their clinical application requires careful monitoring and management.