Corticosteroids exert immunosuppressive effects by which mechanism?

• A. Suppressing inflammatory gene expression and reducing cytokine production
• B. Inhibiting phagocytosis by macrophages exclusively
• C. Directly killing lymphocytes by cytotoxic effects
• D. Blocking all antibody production entirely

Answer: (A)

Corticosteroids suppress the immune response mainly by changing gene expression in immune cells to lower inflammatory mediators. Inside cells, they bind the glucocorticoid receptor; this complex then moves to the nucleus and represses transcription of pro-inflammatory genes, largely by inhibiting NF-κB and AP-1 pathways. As a result, production of key cytokines such as IL-1, IL-6, TNF-α, and IL-2 drops, along with chemokines and enzymes like COX-2. They also upregulate anti-inflammatory proteins like annexin-1, which further reduces inflammation by blocking processes such as phospholipase A2. The net effect is diminished cytokine signaling, reduced leukocyte recruitment and activation, and less antigen presentation. This central mechanism—suppressing inflammatory gene expression and cytokine production—best explains the immunosuppressive action of corticosteroids. They do not primarily inhibit phagocytosis exclusively, nor do they kill lymphocytes directly at typical doses, and they do not completely block antibody production.