What causes an increase in Interleukin-8 (IL-8)?

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Last updated: June 12, 2025View editorial policy

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From the Guidelines

Interleukin-8 (IL-8) levels increase in response to various inflammatory stimuli and pathological conditions, including bacterial and viral infections, tissue damage, trauma, and oxidative stress, as well as in certain autoimmune diseases and environmental exposures. The primary triggers for IL-8 production include:

  • Bacterial and viral infections, which activate pattern recognition receptors like Toll-like receptors on immune cells 1
  • Tissue damage and trauma, which stimulate IL-8 production through damage-associated molecular patterns 1
  • Pro-inflammatory cytokines such as TNF-α and IL-1β, which strongly induce IL-8 secretion from various cell types including epithelial cells, endothelial cells, and leukocytes 1
  • Oxidative stress conditions with increased reactive oxygen species, which activate transcription factors like NF-κB that upregulate IL-8 expression 1
  • Hypoxia, which triggers IL-8 production through HIF-1α pathways 1
  • Certain autoimmune diseases, which feature elevated IL-8 levels due to dysregulated immune responses 1
  • Environmental factors including cigarette smoke, air pollutants, and UV radiation, which can stimulate IL-8 production in exposed tissues 1
  • Some tumors, which constitutively produce high IL-8 levels to promote angiogenesis and metastasis 1 Understanding these mechanisms is important because IL-8 serves as a potent neutrophil chemoattractant and activator, orchestrating acute inflammatory responses and contributing to chronic inflammatory conditions when persistently elevated 1.

From the Research

Causes of Increased IL-8

  • Tumors, particularly solid tumors, can produce large quantities of IL-8, which can promote angiogenesis, recruit immunosuppressive cells, and stimulate epithelial-to-mesenchymal transition, leading to increased IL-8 levels 2
  • Inflammation can cause an increase in IL-8 production, as it is a chemoattractant cytokine that attracts and activates neutrophils in inflammatory regions 3
  • IL-8 can be produced by various types of cells, including monocytes, macrophages, and endothelial cells, in response to stimuli such as IL-1 and TNFα 4
  • Hematologic malignancies can also lead to increased levels of IL-8, as well as other inflammatory markers such as NLR, PLR, and SII 5
  • Cancer development and progression can be associated with increased IL-8 levels, which can contribute to immunotherapy resistance 6

Factors that Contribute to Increased IL-8

  • Tumor size and type, with larger and more aggressive tumors tend to produce more IL-8 2
  • Inflammatory stimuli, such as IL-1 and TNFα, which can induce IL-8 production 4
  • Presence of immunosuppressive cells, such as neutrophils and myeloid-derived suppressor cells, which can be recruited by IL-8 2
  • Epithelial-to-mesenchymal transition, which can be stimulated by IL-8 and contribute to cancer progression 4
  • Systemic inflammatory response, which can be reflected by elevated levels of inflammatory markers such as NLR, PLR, and SII 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Significance of the IL-8 pathway for immunotherapy.

Human vaccines & immunotherapeutics, 2020

Research

The role of IL-8 in cancer development and its impact on immunotherapy resistance.

European journal of cancer (Oxford, England : 1990), 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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