Interleukin-15 (IL-15) is a pro-inflammatory cytokine that plays a vital role in regulating immune cell activation, proliferation, and survival. Produced primarily by monocytes, macrophages, and epithelial cells, IL-15 supports both innate and adaptive immune responses, helping the body respond to infections and maintain long-term immune readiness.

While IL-15 shares many biological functions with IL-2, it has a broader impact on natural killer (NK) cells and CD8+ T lymphocytes, two immune cell types critical for detecting and eliminating infected or damaged cells. This makes IL-15 a central regulator of cell-mediated immunity—the branch of the immune system responsible for direct cellular defense.


Biological Function

IL-15 contributes to immune defense and regulation through several key mechanisms:

  • Activates and sustains NK cells that target infected or tumor cells

  • Supports CD8+ T-cell proliferation and survival, aiding in long-term immune memory

  • Enhances production of interferon-gamma (IFN-γ), amplifying immune responses

  • Promotes tissue repair and regeneration following inflammation or injury

  • Coordinates communication between innate and adaptive immunity, helping fine-tune inflammatory balance

IL-15 is normally present in low concentrations but rises during infection, inflammation, or immune stress. This ensures a strong, localized defense response—while excessive IL-15 activity can contribute to chronic inflammation or autoimmunity.


Elevated IL-15 Levels

High IL-15 levels often indicate immune system activation and can reflect ongoing inflammation, infection, or autoimmune processes. When IL-15 remains persistently elevated, it can lead to immune hyperactivity and tissue damage due to prolonged stimulation of T and NK cells.

Common associations with elevated IL-15 include:

  • Autoimmune diseases, such as rheumatoid arthritis, celiac disease, multiple sclerosis, and type 1 diabetes, where IL-15 promotes autoreactive immune cell survival

  • Chronic viral infections, including HIV, hepatitis, and Epstein-Barr virus (EBV), which trigger ongoing immune activation

  • Inflammatory disorders, including inflammatory bowel disease (IBD) and psoriasis

  • Cancer-related inflammation, as IL-15 can enhance cytotoxic immune activity in tumor environments

  • Exercise or stress-related immune activation, where IL-15 may temporarily rise as part of metabolic and muscular adaptation

Sustained IL-15 elevation can amplify Th1-type immune responses, often seen in autoimmune or inflammatory conditions marked by excessive immune activation.


Low IL-15 Levels

Reduced IL-15 levels may indicate suppressed immune signaling, poor NK or T-cell function, or impaired cytokine communication. Low IL-15 can weaken cellular immune defense and lower resilience against infections or tumors. It may also be seen in states of malnutrition, chronic stress, or immunosuppressive therapy.


IL-15 in the Cytokine Response Profile (CytoDx)

Within the Cytokine Response Profile (CytoDx) by Diagnostic Solutions Laboratory, IL-15 is measured as part of the pro-inflammatory cytokine panel that reflects Th1 immune activity and cell-mediated defense. Elevated IL-15 levels, especially when accompanied by markers like IFN-γ, IL-2, and TNF-α, can indicate a Th1-dominant immune response—a pattern often linked to chronic inflammation or autoimmune disorders.

By assessing IL-15 alongside other cytokines, clinicians can better understand whether inflammation stems from immune overactivation, infection recovery, or metabolic stress, guiding targeted interventions to rebalance immune function.


Clinical Insights

  • High IL-15: Indicates immune activation or chronic inflammation; often linked to autoimmune disease or persistent infection.

  • Low IL-15: Suggests impaired immune signaling or reduced NK/T-cell activity.

  • Balanced IL-15: Reflects healthy immune readiness and regulation between activation and tolerance.


Supporting Healthy IL-15 Balance

Because IL-15 is sensitive to cellular stress and immune signaling, supporting balanced immune activity may include:

  • Anti-inflammatory nutrition: omega-3 fatty acids, antioxidants, and phytonutrients that reduce chronic immune activation

  • Adequate sleep and stress reduction: cortisol imbalance can dysregulate cytokine production, including IL-15

  • Regular moderate exercise: supports NK cell health and cytokine balance

  • Addressing underlying triggers: chronic infection, autoimmune activity, or environmental stressors that drive IL-15 elevation


Summary

IL-15 (Interleukin-15) is a pivotal cytokine that bridges innate and adaptive immunity by activating NK cells and T lymphocytes. Elevated IL-15 levels often reflect chronic immune activation or autoimmune signaling, while low levels may indicate suppressed immune function. Within the Cytokine Response Profile (CytoDx) by Diagnostic Solutions Laboratory, IL-15 provides critical insight into cell-mediated immunity, helping clinicians pinpoint the root causes of chronic inflammation and immune imbalance.

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