How does cortisol affect the immune system?

Effects of Cortisol on the Immune System

Cortisol has profound immunosuppressive effects on both innate and adaptive immunity, inhibiting cytokine production, suppressing T-cell proliferation, and altering B-cell function, though paradoxically it can enhance certain immune responses in specific contexts.

Primary Immunomodulatory Effects of Cortisol

Cortisol affects multiple components of the immune system:

Effects on Cellular Immunity

• T-cell suppression: Cortisol significantly decreases CD4+ and CD8+ T-cell counts, with effects appearing as early as the first week of corticosteroid treatment 1
• Cytokine inhibition: Acts as a potent inhibitor of multiple cytokines including interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor (TNF), and gamma interferon 2
• Blocks T-cell proliferation: Inhibits antigen-induced T-cell proliferation, particularly affecting memory T-cell formation and function 2

Effects on Humoral Immunity

• B-cell modulation: While initially less affected than T-cells, B-cells show prolonged suppression that may persist for months after cortisol exposure ends 1
• Antibody production: Impairs B-cell function and antibody production through inhibition of IL-4 and IL-5 production by T-cells 2
• Hypogammaglobulinemia: Can lead to reduced immunoglobulin levels, increasing susceptibility to infections 2

Effects on Innate Immunity

• Neutrophil effects: Induces neutrophilic leukocytosis while simultaneously causing lymphopenia and eosinopenia 1
• Inflammatory mediator suppression: Reduces production of proinflammatory mediators and antimicrobial peptides 3
• Increased infection risk: Suppresses immune system function, increasing risk of infection with bacterial, viral, fungal, protozoan, or helminthic pathogens 4

Temporal Dynamics of Cortisol's Immune Effects

Cortisol's effects on immunity follow a biphasic pattern:

1. Acute effects (hours to days):

   • Immediate immunosuppression
   • Reduction in inflammatory cytokine production
   • Decreased T-cell function 5

2. Delayed effects (days to weeks):

   • Potential immune stimulation in certain contexts
   • Enhanced interferon-γ-mediated proinflammatory responses
   • Increased expression of interferon-γ receptor type 1 5

Paradoxical Immune Enhancement

Despite its primarily immunosuppressive role, cortisol can enhance certain immune responses:

• Proinflammatory interactions: Cortisol can augment interferon-γ-mediated proinflammatory responses in human mononuclear phagocytes 5
• Receptor upregulation: Increases expression of interferon-γ receptor type 1 on monocytes/macrophages 5
• Cytokine modulation: While suppressing many cytokines, cortisol can enhance production of specific proinflammatory mediators like CCL20 6

Clinical Implications

Infection Risk

• Increased susceptibility: Patients on corticosteroid therapy have higher risk of infections, particularly bacterial infections 2
• Reactivation of latent infections: Can reactivate tuberculosis, hepatitis B, and other latent infections 4
• Masking of infection signs: May suppress fever and other inflammatory signs, making infections harder to detect 4

Vaccination Response

• Reduced vaccine efficacy: Patients on corticosteroids may have impaired responses to vaccines 2
• Timing considerations: Vaccination is more effective before starting corticosteroid therapy or after discontinuation 2

Stress-Related Immune Modulation

• Stress response: Cortisol release during stress can alter immune function, potentially increasing susceptibility to respiratory infections 6
• Perceived stress: Higher perceived stress correlates with altered monocyte function and systemic cytokine levels 6

Monitoring and Management

For patients on corticosteroid therapy:

• Infection prophylaxis: Consider antimicrobial prophylaxis for patients on high-dose corticosteroids (≥1 mg/kg) 2
• Tuberculosis screening: Test for tuberculosis before initiating additional immunosuppressive therapy 2
• Vaccination timing: Administer vaccines before starting corticosteroid therapy when possible 2
• Tapering: Gradually reduce corticosteroid doses to prevent adrenal insufficiency and allow immune recovery 4

Special Considerations

• Transplant recipients: Particularly vulnerable to immunosuppressive effects of cortisol and other immunosuppressants 2
• Autoimmune conditions: Balance between controlling inflammation and avoiding infection risk 2
• Chronic stress: Prolonged cortisol elevation may lead to different immune effects than acute elevation 2

Cortisol's complex effects on immunity highlight the delicate balance between beneficial anti-inflammatory actions and potentially harmful immunosuppression, requiring careful clinical consideration when using corticosteroids therapeutically.