Comprehensive Review Maps Interleukin-8's Pleiotropic Roles Across Autoimmune, Cancer, and Inflammatory Diseases

Cytokines are crucial mediators of cell-to-cell communication in both healthy and diseased states, serving as detectable biomarkers and potential drug targets. Among these, Interleukin-8 (IL-8) has emerged as a central player in the pathogenesis of numerous immunological disorders. These include autoimmune pathologies, sepsis, neurological, liver, and cardiovascular diseases, as well as various solid cancers. Despite its widespread involvement, a single comprehensive review integrating IL-8's roles across all these diverse fields has been lacking, creating a gap in understanding its full therapeutic and diagnostic potential.

This comprehensive review synthesized existing preclinical and clinical evidence on Interleukin-8 biology and function across various disease domains. Researchers systematically analyzed published literature to characterize IL-8's involvement in non-malignant conditions, including inflammatory bowel diseases, sepsis, neuroinflammation, liver, and cardiovascular pathologies. The review also detailed IL-8's pro-tumorigenic roles in oncology, its impact on the immunosuppressive microenvironment, and implications for direct/indirect IL-8 targeting, alongside the involvement of the gut microbiota. The aim was to provide a unified understanding of IL-8's multifaceted contributions to health and disease.

The review confirmed Interleukin-8 (IL-8) as a pleiotropic cytokine with a central role in the pathogenesis of a wide array of conditions. In non-malignant diseases, IL-8 is deeply implicated in inflammatory bowel diseases, sepsis, neuroinflammation, and various liver and cardiovascular pathologies, acting as a key mediator of inflammation and tissue damage. In oncology, IL-8 not only serves as a significant prognostic biomarker but also functions as a predictive tool in several solid cancers, influencing disease progression and therapeutic response. The review highlighted IL-8's pro-tumorigenic roles, including its ability to shape an immunosuppressive microenvironment that aids cancer growth and metastasis. Furthermore, increasing evidence positions IL-8 as a crucial prognostic/predictive biomarker for immunotherapy, enabling stratification of eligible patients to avoid unnecessary toxicity and disease progression. The review also discussed the implications of direct and indirect targeting of IL-8, and its complex interplay with the gut microbiota in both inflammatory and oncological contexts.

IL-8's utility as a prognostic and predictive biomarker extends to immunotherapy, offering a means to stratify patients and optimize treatment strategies.