How does hydrocortisone (cortisol) impact the immune system?

Hydrocortisone's Impact on the Immune System

Hydrocortisone significantly suppresses the immune system through multiple mechanisms, including inhibition of inflammatory cytokines, reduction of lymphocyte populations, and disruption of immune cell signaling pathways. 1

Primary Immunosuppressive Effects

• Hydrocortisone inhibits the production of key cytokines including interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor (TNF), and gamma interferon, which blocks antigen-induced T-cell proliferation 2
• It suppresses both T-cell and B-cell responses through blockage of cellular proliferation after antigen stimulation and inhibition of cytokine production necessary for immune activation 2
• Hydrocortisone specifically inhibits IL-4 production at both the protein and mRNA levels, which partially explains its effectiveness in treating allergic conditions 3
• It causes a significant decline in circulating B and T cell subsets, reaching their lowest levels 4-8 hours after administration 4

Molecular Mechanisms

• Transcriptome analysis reveals that hydrocortisone downregulates NF-κB signaling, apoptosis, and cell death signaling pathways 4
• It enhances glucocorticoid receptor signaling transcripts while simultaneously activating natural killer (NK) cell pathways 4
• At low doses, hydrocortisone may paradoxically enhance certain immune responses, demonstrating a dose-dependent effect 2
• High-dose corticosteroids have been associated with increased overall mortality and increased mortality from secondary infections in clinical studies 2

Differential Effects on Immune Cell Populations

• B and T lymphocytes typically rebound above baseline levels 24 hours after hydrocortisone administration, while NK cell numbers remain relatively stable throughout treatment 4
• Hydrocortisone reduces the immunosuppressive function of NK cells in trauma models, potentially through upregulation of glucocorticoid-induced tumor necrosis factor receptor-ligand on dendritic cells 5
• Animal studies demonstrate that hydrocortisone markedly suppresses normal immune responses to antigens, with decreased numbers of RFC cells and B lymphocytes in peripheral blood 6

Clinical Implications

• Patients on corticosteroid therapy have decreased resistance to infections and may have difficulty localizing infections due to masked inflammatory signs 1
• Hydrocortisone can increase susceptibility to opportunistic infections, including fungal, viral, and bacterial pathogens 2
• Individuals receiving hydrocortisone should not be vaccinated against smallpox, and other immunization procedures may be less effective due to potential neurological complications and reduced antibody response 1
• Prophylaxis against infections like Pneumocystis jirovecii pneumonia should be considered in patients receiving prednisone equivalent of ≥20 mg/day for 4 or more weeks 2

Special Considerations

• Patients with latent tuberculosis require close monitoring as hydrocortisone may cause reactivation of the disease 1
• Individuals on corticosteroids are at higher risk for severe or fatal courses of infections like chickenpox and measles 1
• Hydrocortisone may decrease interleukin-10 levels, which can be beneficial in trauma-induced immunosuppression by preventing dendritic cell elimination by NK cells 5
• Baseline corticosteroid therapy (≥10 mg prednisone equivalent daily) has been associated with poorer outcomes from immune checkpoint inhibitor therapy in cancer patients 2

Monitoring and Management

• Blood glucose monitoring is recommended for patients on hydrocortisone therapy due to potential hyperglycemia 2
• Patients on prolonged corticosteroid therapy may benefit from prophylaxis against fungal infections and zoster reactivation 2
• Calcium and vitamin D supplementation is recommended to reduce the risk of osteoporosis during extended hydrocortisone treatment 2
• Careful monitoring for opportunistic infections is essential, especially when hydrocortisone is combined with other immunosuppressive agents 2

Understanding hydrocortisone's complex effects on the immune system is crucial for optimizing therapeutic use while minimizing potential complications from immunosuppression.