Another area requiring further exploration is the geographical variability in immune responses among different ethnic groups. This is particularly complex in today’s era of increased global migration and subsequent exposure to diverse immune triggers [38].

The number of patients included in studies varied significantly, ranging from 12 in Wu’s study to 112 in Watanabe’s. Furthermore, different methodologies were used to assess IL-8, including immunologic, genetic, transcriptomic, and enzymatic assays. Samples were obtained from nasal challenges, sinus and nasal tissue explants, serum, and nasal secretions, making systematic comparisons difficult. Local allergic rhinitis is another topic that requires further investigation regarding the molecular interplay and the connection with interleukin 8. This new approach is focusing on personalized medicine in allergies [39]. One limitation of our analysis is that we focused on IL-8 in relation to allergic rhinitis (AR) and chronic rhinosinusitis (CRS), excluding asthma within the broader context of united airway disease theory. Since Crossman introduced the idea of “the same airway, the same disease” in 1997, research in this field has grown, and the connection between the upper- and lower-airways is now widely recognized. While it is challenging to delineate the specific mechanisms of interaction between asthma and various upper-airway conditions like AR and CRS through a single theory, several overlapping mechanisms may contribute to this pathological phenomenon. United airway disease (UAD) describes the coexistence of upper- and lower-airway diseases as a unified entity, emphasizing their shared pathological traits. Increasing evidence highlights the complexity of UAD, which includes multiple phenotypes and endotypes as well as various respiratory diseases. The coexistence of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently noted; approximately 40% to 70% of patients with CRSwNP also experience asthma, which correlates with more severe sinonasal symptoms. Conversely, CRSwNP is present in 10% to 30% of mild asthma cases but can rise to 70% to 90% among those with severe asthma, often associated with poorer outcomes. Common pathophysiological mechanisms underpinning CRSwNP and asthma exist, with the type 2 (T2) endotype being the most prevalent. Acknowledging that a single biomarker may not capture the complexity of UAD, recent studies have explored combinations of biomarkers to create composite scores that could enhance predictive accuracy. Endotypes for airway diseases include type 1 (mediated by IFN-γ, IL-2, and lymphotoxin-α), type 2 (involving IL-4, IL-13, IL-5, and immune cells like eosinophils and mast cells), and type 3 (driven by neutrophilia and TH17 cells). This focus aligns with our expertise in allergology and ENT, aimed at examining the role of IL-8 in upper-respiratory inflammatory responses [40,41]. Applying Artificial Intelligence (AI) to the field of allergies helps investigators expand their understanding of disease pathogenesis, improve diagnostic accuracy, enable prediction for treatments and outcomes, and for drug discovery. Incorporating data regarding interleukin 8 in AI algorithms can accelerate the research process [42]. Biological treatment is the future for the management of this pathology. Current biological treatment compounds are focusing on interleukins (IL) IL-4, IL-5, and IL-13. Interleukin 8 could be a future candidate for the selective action of future biologic treatment [43]. There are other allied specialties that could benefit from extended research of the IL-8 molecular interplay. Current data analyzed the implications of IL-8 related mechanisms in the dry eye disease (DED) and ocular allergy (OA). IL-8 is another key chemokine that has been consistently increased in DED patients. Moreover, IL-8, IL-2, IFN-γ, and EGF may represent biomarkers of disease gravity in DED [44]. The possible clinical application of specific cytokines and chemokines contributing to tumorigenesis and the clinical outcome of several cancers has been reported. Pro-inflammatory cytokines IL-6 and IL-8 are potential biomarkers for cancer pathogenesis and could serve as markers of disease progression [45]. Sports medicine is another domain where further analysis of IL-8 could offer insight regarding the prevalence of exercise-induced bronchoconstriction (EIB) and also to investigate the effect of myokines in the performance of marathon runners [46]. The recent COVID-19 pandemics accelerated the research of the possible notable connection between IL-8 and viral responses, with circulating levels of IL-8 and soluble IL-2Rα being strongly associated with the duration of illness in patients with severe COVID-19 [47]. To better understand IL-8’s role in the atherosclerotic process and explore evidence supporting its causal involvement, cardiologists have examined the relationship between IL-8 levels and carotid intima-media thickness (c-IMT), a marker of vascular remodeling indicative of subclinical atherosclerosis. Elevated plasma IL-8 levels were found to correlate with increased c-IMT, suggesting a link to subclinical atherosclerosis [48]. Macrolides, commonly used as anti-inflammatory agents in respiratory conditions, have shown an off-target effect of inhibiting IL-8. This effect is thought to contribute to the reduced airway inflammation observed in patients undergoing chronic azithromycin therapy for airway diseases, such as chronic rhinosinusitis, where IL-8 levels correlate with disease severity and neutrophil infiltrates [49]. IL-8 also plays a role in lupus nephritis, a rare autoimmune disorder. In this condition, inflammatory cytokines like IL-6, IL-8, IL-1β, IFNα, IFNγ, and IP-10 are elevated in serum, and the transcriptional levels of interferon-stimulated genes are significantly higher [50]. Additionally, in Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), IL-8 levels in cerebrospinal fluid (CSF) can help distinguish between the two. Patients with CSF IL-8 levels exceeding 70 pg/mL are more likely to have acute inflammatory demyelinating polyneuropathy (AIDP) rather than acute-onset CIDP, suggesting its potential as a diagnostic marker [51].