Interleukin-8 in health and disease.

Cytokines are among the main factors involved in indirect cell-to-cell communication in physiological and pathological conditions. In this way, cytokines are soluble and tissue-resident easily detectable biomarkers for the diagnosis and the prediction of clinical outcome, as well as drug targets. Over the years, the pleiotropic IL-8 gained a central role in the pathogenesis of several immunological disorders, spanning from autoimmune pathologies and sepsis to neurological, liver and cardiovascular diseases. In several solid cancers, IL-8 not only serves as a prognostic biomarker but also as predictive tool. Increasing evidence highlighted IL-8 as a prognostic/predictive biomarker even for immunotherapy to stratify eligible patients, to avoid unnecessary toxicity and progression. Today, a comprehensive review covering IL-8 in all these fields has not yet been published. Hence, we aim to provide preclinical and clinical evidence on the biology and functions of IL-8, involved in the pathogenesis of non-malignant diseases, including inflammatory bowel diseases, sepsis, neuroinflammation, liver and cardiovascular pathologies. In oncology area, we will describe the pro-tumorigenic roles, including the characterization of the immunosuppressive microenvironment, also discussing the implications of direct/indirect IL-8 targeting and the involvement of gut microbiota. Unfortunately, the main obstacles to establish IL-8 as a useful non-invasive clinical tool for diagnosis and treatments' selection are the lack of the standardization of method detection and the source of IL-8 production.