From the Guidelines
IL-8 plays a crucial role in the immune system by attracting neutrophils to sites of inflammation, and its elevation is associated with various inflammatory conditions, including chronic lung disease of infancy and adult onset Still's disease, as evidenced by studies such as 1 and 1. The role of Interleukin-8 (IL-8) is multifaceted, involving the attraction of neutrophils to sites of inflammation, which is a key component of the immune response. IL-8 is produced by various cells, including macrophages, epithelial cells, and endothelial cells, in response to inflammatory stimuli such as bacterial products, viruses, and pro-inflammatory cytokines like TNF-α and IL-1.
- IL-8 functions by binding to the CXCR1 and CXCR2 receptors on neutrophils, promoting their migration and activation.
- This chemokine is particularly important in acute inflammatory responses and is elevated in many inflammatory conditions, including bacterial infections, inflammatory bowel disease, psoriasis, and certain types of cancer, as noted in studies like 1.
- Excessive or prolonged IL-8 production can contribute to chronic inflammation and tissue damage, highlighting the need for careful management of conditions where IL-8 plays a significant role, as suggested by research such as 1. In clinical settings, IL-8 levels can sometimes be measured as a biomarker of inflammation, though this is not routinely done in most practice settings.
- Targeting IL-8 or its receptors represents a potential therapeutic strategy for inflammatory diseases, with several inhibitors currently under investigation in clinical trials, indicating a promising area of research for the management of IL-8 related conditions. The importance of IL-8 in inflammatory processes is further underscored by its involvement in conditions like chronic lung disease of infancy, where it is increased in the bronchoalveolar lavage fluid of affected infants, as reported in 1. Similarly, in adult onset Still's disease, IL-8 levels are persistently raised, even in disease remission, as observed in 1, suggesting its role in the chronic inflammation characteristic of these diseases.
From the Research
Role of Interleukin-8 (IL-8)
- IL-8 is a chemoattractant cytokine that plays a significant role in inflammation by attracting and activating neutrophils in inflammatory regions 2
- It has a distinct target specificity for neutrophils, with only weak effects on other blood cells 2
- IL-8 is associated with poor outcome in patients with advanced cancers treated with immune-checkpoint inhibitors, and its elevated levels are linked to enhanced intratumor neutrophils 3, 4
- High levels of IL-8 in plasma, peripheral blood mononuclear cells, and tumors are associated with decreased efficacy of atezolizumab in patients with metastatic urothelial carcinoma and metastatic renal cell carcinoma 3
- IL-8 favors pro-inflammatory activity of human monocytes/macrophages by reducing the expression of CD16 and CD124, and enhancing the expression of CD119 and CD197 5
- IL-8 is also involved in the pathogenesis of rheumatoid arthritis, promoting the detrimental activation of immune and stromal cells in the synovial membrane, tendons, and extra-articular sites 6
Mechanisms of IL-8
- IL-8 is produced by a variety of tissue and blood cells, including myeloid cells 3
- It is a member of the Interleukin-8 supergene family, which includes other small chemotactic peptides with structural homology 2
- IL-8 shares DNA sequence features with other cytokines, suggesting common regulatory pathways 2
- Its expression is regulated by various mechanisms, including transcriptional and post-transcriptional regulation 2
Clinical Implications
- Elevated serum IL-8 levels are associated with poor prognosis in advanced cancers, and may serve as an independent biomarker in patients receiving immune-checkpoint inhibitors 4
- Therapies that can reverse the impacts of IL-8-mediated myeloid inflammation may be essential for improving outcomes of patients treated with immune checkpoint inhibitors 3
- Targeting IL-8 may improve the management of treatment resistance in patients with rheumatoid arthritis 6