Search Results (1,431)

Rising ocean temperatures due to climate change, combined with the intensification of anthropogenic activity, may lead to changes in the physiology and distribution of native species. Compounding climate stress, microplastic particles (MPs) enter the oceans through wastewater and the breakdown of macroplastics. Depending on their composition, they can be harmful and act as a vehicle for toxic substances, although their effects on native Antarctic and subantarctic species are unknown. Notothenioid fish are members of this group and are found inside and outside Antarctica, such as the Harpagifer, which has adapted to the cold and is particularly sensitive to thermal increases. Here, we aimed to evaluate the innate immune response in the head kidney, spleen, and foregut of two notothenoid fish, Harpagifer antarcticus and Harpagifer bispinis, exposed to elevated temperatures and PVC (polyvinyl chloride) microplastics. Adults from both species were collected on King George Island (Antarctica) and Punta Arenas (Chile), respectively. Specimens were assigned to a control group or exposed to a temperature increase (TI) or PVC microplastics (MPs), separately or in combination (MPs + TI). MP exposures were oral (gavage) for 24 h or aqueous (in a bath) for 24 and 48 h. Using real-time qPCR, we evaluated the relative gene expression of markers involved in the innate immune response, including tlr2 (toll-like receptor 2), tlr4 (toll-like receptor 4), myd88 (myeloid differentiation factor 88), nfkb (nuclear factor kb), il6 (interleukin 6), and il8 (irterleukin 8). We found differences between treatments when H. antarcticus and H. bispinis were exposed independently to MPs or thermal increase (TI) in the experiment with a cannula, showing an up-regulation in transcripts. In contrast, a down-regulation was observed when exposed in combination to MP + TI, which looked to be tissue-dependent. However, transcripts related to innate immunity in the bath experiment increased when exposure to both stressors was combined, mostly at 48 h. These results highlight the importance of evaluating the effects of multiple stressors, both independently and in combination, and whether these species will have the capacity to adapt or survive under these conditions, especially in waters where temperature is increasing and pollution is also rising, primarily from MP-PVC, a plastic widely used in various industries and among the population. Full article

Polyporusterone B, a triterpene carboxylic acid isolated from Polyporus umbellatus Fries, exhibits anti-cancer and anti-hemolytic activities; however, its anti-inflammatory properties and underlying mechanisms remain unelucidated. We studied the anti-inflammatory effects of Polyporusterone B using lipopolysaccharide (LPS)-stimulated Raw264.7 murine macrophages (in vitro) and LPS-induced endotoxin shock in C57BL/6 mice (in vivo). Results showed that Polyporusterone B (1, 5, and 10 μM) had no cytotoxicity toward Raw264.7 cells, but significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6)) in a concentration- and time-dependent manner, as demonstrated by Griess assay, qPCR, and ELISA. Western blot analysis revealed that Polyporusterone B suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (ERK, P38, and NK) and reduced phosphorylation-mediated degradation of inhibitor of κBα (IκBα). Immunofluorescence and immunohistochemical staining further confirmed that Polyporusterone B blocked nuclear translocation of nuclear factor kappa-B (NF-κB)/Rel A in both Raw264.7 cells and mouse tissues. In the in vivo model, Polyporusterone B pretreatment significantly mitigated LPS-induced multi-organ pathological damage (e.g., lung edema, hepatic inflammation, renal hemorrhage) and downregulated tissue levels of TNF-α, IL-1β, and IL-6. These findings suggest that Polyporusterone B exerts anti-inflammatory effects by inhibiting the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, suggesting its potential as a therapeutic candidate for inflammatory diseases. Full article

Background/Objectives: The advent of biologics targeting key inflammatory pathways has significantly advanced psoriasis treatment. Among them, the Interleukin-23 inhibitors Guselkumab and Risankizumab have demonstrated high efficacy and rapid clinical response in both clinical trials and real-world studies. However, up to 30% of patients fail to respond. This study aimed to identify pharmacogenetic markers associated with treatment response using a genome-wide association study (GWAS) and protein network-based approach. Methods: Fifty-three patients of Greek origin with moderate-to-severe plaque psoriasis were treated with Guselkumab or Risankizumab. Based on Psoriasis Area and Severity Index (PASI) improvement at 3 and 6 months, patients were categorized as responders or non-responders. Approximately 730,000 single-nucleotide polymorphisms (SNPs) were genotyped. After filtering, a GWAS was performed to identify variants associated with treatment response. Additionally, protein–protein interaction (PPI) network analysis was applied to the two Interleukin-23 subunits and SNPs within or near genes encoding Interleukin-23-interacting proteins to test for their association. Results: The GWAS identified two novel variants, rs73641950 and rs6627462, significantly associated with treatment response, with both surpassing the genome-wide significance threshold after Bonferroni correction. The PPI-based approach revealed rs13086445, located downstream of the Interleukin-12 subunit alpha (IL12A) gene, as another associated variant. All three SNPs lie in genomic regions with potential regulatory roles. Conclusions: This study identifies three novel genetic variants associated with response to Interleukin-23 inhibitors in psoriasis. These findings provide promising pharmacogenetic markers which, upon validation in larger, independent cohorts, will enable the translation of a patient’s genotype into a response phenotype, thereby guiding clinical decisions and improving drug effectiveness. Full article

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a serious health problem worldwide. Moreover, increased systemic and cerebrovascular inflammation is one of the major pathophysiological features of T2DM, and a growing body of evidence emphasizes T2DM with memory and executive function decline. Bioactive sphingolipids regulate a cell’s survival, inflammatory response, as well as glucose and insulin signaling/metabolism. Moreover, current research on the role of sphingosine kinases (SPHKs) and sphingosine-1-phosphate receptors (S1PRs) in T2DM is not fully understood, and the results obtained often differ. The aim of the present study was to evaluate the effect of metformin (anti-diabetic agent, MET) on the brain’s sphingosine-1-phosphate-related signaling and ultrastructure in diabetic mice. Our results revealed elevated mRNA levels of genes encoding sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate receptor 3 (S1PR3), which was accompanied by downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) in the hippocampus of diabetic mice. Simultaneously, upregulation of genes encoding pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was observed. Administration of MET significantly reversed changes in mRNA levels in the hippocampus and reduced Sphk2, Il6, and Tnf, with concomitant upregulation of S1pr1 gene expression. Ultrastructural analysis of diabetic mice hippocampus revealed morphological alterations in neurons, neuropil, and capillaries that were manifested as mitochondria swelling, blurred synaptic structure, and thickened basal membrane of capillaries. The use of MET partially reversed those changes. Our research emphasizes the important role of insulin sensitivity modulation by metformin in the regulation of SPHKs and S1PRs and inflammatory gene expression in a murine model of T2DM. Full article

Background: Interleukin-6 (IL-6) is a multifunctional cytokine implicated in various inflammatory and immune-mediated processes. Its involvement in systemic lupus erythematosus (SLE) has been increasingly investigated, particularly related to disease activity and tissue damage. This study aimed to quantify serum IL-6 levels in patients with SLE and assess their associations with clinical manifestations and laboratory parameters. Methods: A total of 88 patients diagnosed with SLE and 87 matched healthy controls were included. Serum IL-6 concentrations were measured by ELISA. Clinical data, SLEDAI scores, organ involvement, inflammatory markers, and autoantibody profiles were recorded. The statistical analysis involved non-parametric testing, correlation analysis, and linear regression. Results: IL-6 concentrations were higher in SLE patients than in controls (7.46 ± 6.73 vs. 5.30 ± 10.89 pg/mL). Significantly increased IL-6 levels were observed in patients with active disease (SLEDAI ≥ 6; p = 0.025) and renal (p = 0.001) involvement. Positive correlations were identified between IL-6 and ESR, creatinine, ANA, and specific autoantibodies (anti-dsDNA, SSA, and SSB). IL-6 also correlated with IL-10 (p = 0.010) but showed no significant association with IL-17A, TNF-α, CRP, or complement levels. Conclusions: Elevated IL-6 levels are associated with greater disease activity and specific organ involvement in SLE. These findings highlight IL-6 as a measurable indicator of immunological and clinical disease expression, supporting its relevance in disease monitoring. Full article

Radiotherapy employs high-energy X-rays to precisely target tumor tissues while minimizing damage to the surrounding healthy structures. Although its clinical efficacy is well established, the immunomodulatory effects of ionizing radiation remain complex and context-dependent. This study investigated the biological effects of radiotherapeutic doses on immune cells by evaluating lymphocyte viability, phenotypic profiles, and cytokine expression levels. Peripheral blood mononuclear cells (PBMCs) were isolated from six healthy donors and irradiated with 0, 2, or 6 Gy using a 6 MV linear accelerator (LINAC). Dose validation with an ionization chamber demonstrated strong agreement between estimated and measured values (intraclass correlation coefficient = 1, 95% CI). Immune subsets, including T cells (CD3+), helper T cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+CD4+Foxp3+), and natural killer (CD3-CD56+) cells, along with intracellular cytokines interleukin-12 (IL-12) and interferon-gamma (IFN-γ), were analyzed via flow cytometry at multiple time points. The results showed a significant, dose-dependent decline in overall lymphocyte viability (p < 0.01) compared to control. Cytotoxic T cells were the most radiosensitive, followed by helper and regulatory T cells, while NK cells were the most radioresistant. IL-12 expression initially increased post-irradiation, while IFN-γ levels remained variable. These findings demonstrate that radiation induces distinct alterations in immune phenotypes and cytokine profiles, which may shape the immune response. Immune profiling following irradiation may therefore provide valuable insights for optimizing combination strategies that integrate radiotherapy and immunotherapy in cancer treatment. Full article

Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular risk characterized by low-grade inflammation. The aim of this systematic review and meta-analysis was to assess the effects of resistance exercise training (RET) predominantly on cytokines, along with changes in glucose profile and body composition in T2DM patients. The present systematic review and meta-analysis was conducted utilizing PubMed, Web of Science, Embase, and the Cochrane Library databases from their inception up to July 2024 (PROSPERO; registration number CRD420251149352). We screened only for randomized controlled trials investigating the effects of systematic, supervised RET on C-reactive protein (CRP) and adipokines: adiponectin, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), along with changes in anthropometric indices and glycemic control in adult T2DM patients. Pooled post-exercise weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated for all outcomes of interest between exercise-treated patients and controls. Sixteen studies involving a total of 668 T2DM patients were retrieved from the databases for meta-analysis. We used the GRADE framework for assessing the certainty of evidence. Cochran Q-score (I²) was used to estimate heterogeneity among studies (level of significance p < 0.10) and risk of bias analysis was also performed. The cumulative results showed that post-RET inflammatory markers were lower in exercise-treated patients compared to controls regarding CRP (mg/L) (WMD: −0.63; 95%CIs: −1.05, −0.20; p < 0.001); adiponectin (μg/mL) (WMD: −0.94; 95%CIs: −1.49, −0.38; p < 0.001). The results from adiponectin are quite conflicting since they derived from only three studies, where one of them had the greater impact. In parallel, we noticed significant amelioration of fasting glucose and HbA1c (p < 0.001), while body weight remained unaltered. Our meta-analysis demonstrated non-significantly lower levels of IL-6 and TNF-α in RET vs. control group. RET can merely reduce the inflammatory burden in T2DM patients by ameliorating the circulating levels of CRP and adiponectin, while in the rest of the biomarkers, non-significant results were obtained. Hence, the overall clinical impact of those anti-inflammatory effects of RET needs to be determined. Full article

Osteoarthritis (OA) is primarily a degenerative disease triggered by joint inflammation and oxidative stress. While Aster glehni is an edible and traditionally medicinal herb, the beneficial effect of A. glehni on OA progression remains unknown. This study aimed to investigate the effect of A. glehni extract (AGE) and its primary biological compound—3,5-dicaffeoylquinic acid (3,5-DCQA)—on inflammation and oxidative stress in chondrocytes. AGE effectively inhibited the expression of interleukin (IL)-6, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, and MMP-13 in chondrocytes stimulated by IL-1β for 24 h. In contrast, 3,5-DCQA did not inhibit IL-6, COX-2, and MMP expressions under the same conditions. However, when chondrocytes were stimulated by IL-1β for a short duration (6 h), 3,5-DCQA suppressed IL-6, COX-2, and MMP expressions. The inhibition of IL-6, COX-2, and MMP expressions by AGE was associated with the p38 kinase and nuclear factor-κB signaling pathways, but not ERK and JNK signaling pathways. Furthermore, AGE prevented cell apoptosis and reduced intracellular reactive oxygen species levels in chondrocytes induced by hydrogen peroxide (H₂O₂). AGE restored the decreased superoxide dismutase 1 and catalase mRNA expressions caused by H₂O₂. Collectively, AGE may protect against cartilage deterioration by inhibiting inflammation and oxidative stress, making it a promising therapeutic agent for alleviating OA. Full article

Background: Treatment with androgen receptor (AR) signaling inhibitors, such as enzalutamide, can induce neural lineage plasticity in prostate cancer, potentially progressing to t-NEPC. However, the molecular mechanisms underlying this enzalutamide-driven plasticity, particularly the contribution of immune signaling pathways, remain poorly understood. Methods: We analyzed transcriptomic profiles of patient samples and prostate cancer cell lines to investigate changes in immune signaling pathways. Interferon gamma (IFNγ), interferon alpha (IFNα), and interleukin 6 (IL6)-Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signaling were assessed in enzalutamide-sensitive and -resistant prostate cancer cells. Functional assays were conducted to examine cell responsiveness to cytokine stimulation and susceptibility to STAT1 inhibition using fludarabine. Results: Immune-related pathways, including IFNγ, IFNα, IL6-JAK-STAT3, and inflammatory responses, were significantly suppressed in NEPC patient samples compared to those with castration-resistant prostate cancer (CRPC). Enzalutamide-resistant and NEPC cells exhibited markedly impaired IFNγ and IL6 signaling. In contrast, early-stage enzalutamide treatment paradoxically enhanced IFNγ and IL6 responsiveness. Transcriptomic profiling revealed coordinated upregulation of E2F target genes and activation of IFNα/IFNγ and JAK/STAT signaling pathways during early treatment. Importantly, these early-stage cells remained highly sensitive to IFNγ and IL6 stimulation and showed increased susceptibility to STAT1 inhibition by fludarabine, a sensitivity that was lost in resistant cells. Conclusions: Early enzalutamide treatment enhances immune responsiveness, while the development of resistance is associated with suppressed immune signaling and increased lineage plasticity. These results suggest a therapeutic window where combining enzalutamide with STAT inhibitors may delay or prevent lineage plasticity and resistance. Full article

Cellular senescence plays a critical role in tumorigenesis and is recognized as a hallmark of colorectal cancer (CRC). Emerging evidence suggests that 5-fluorouracil (5-FU)-induced senescence may contribute to chemoresistance and tumor recurrence. Here, we investigated the effect of 5-FU on colon cancer cell senescence and whether MM-129 (pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine sulfonamide) can antagonize this activity. Senescence was identified by the expression of senescence-associated β-galactosidase (SA-β-gal) and cyclin-dependent kinase inhibitor 1A (p21) using qPCR, microscopy, flow cytometry, and immunohistochemistry. We also measured interleukin 6 (IL-6) and tumor necrosis factor (TNF-α) as key SASP cytokines, along with E-cadherin (CDH1), a marker of epithelial integrity. The SIRT1/STAT3 pathway was evaluated to elucidate the mechanism of MM-129′s action. MM-129 counteracted 5-FU-induced senescence in colon cancer models, reducing p21 levels in zebrafish xenografts and the number of SA-β-gal-positive cells in vitro and in tumor tissues from DLD-1 and HT-29 mouse xenografts. MM-129 also inhibited senescence-associated responses by suppressing SASP cytokines (IL-6, TNF-α) and restoring E-cadherin (CDH1), and it modulated the SIRT1/STAT3 axis, which may underlie the observed senotherapeutic effects. In conclusion, MM-129 represents a novel senotherapeutic candidate. By modulating the SIRT1/STAT3 axis, it may suppress the SASP and weaken pro-survival signaling, thereby facilitating selective clearance of senescent cells. Integrating senotherapeutics with conventional cancer therapies may enhance efficacy and open new avenues for translational research. Full article

Objectives: In this study, our aim is to summarise the available data on the correlation between sarcopenia and sleep disturbances as a consequence of changes in the myokine concentrations. Methods: Our research was conducted by searching through PubMed, Mendeley and Google Scholar. In our analysis, 63 studies are included from the years 2011 to 2025. Among these studies, there are clinical trials, cross-sectional studies, reviews, systematic reviews and meta-analyses. Discussion: There is vast evidence confirming that sleep disturbances are more common among sarcopenic patients. On the other hand, sarcopenia is frequently observed among people with worse quality of sleep. It is also well documented that sarcopenia leads to changes in the myokine serum concentrations, and similar changes are observed among people suffering from sleep disturbances. Sarcopenic patients have lower levels of irisin, BDNF (brain-derived neurotrophic factor), meteorin and IL-15 (interleukin 15) and higher concentrations of FGF-21 (fibroblast growth factor 21) and interleukins 1β, 6 and 10. Lower levels of irisin, BDNF and meteorin, and higher levels of FGF-21 and interleukins 6 and 10, lead to sleep disturbances, like insomnia, reduction of REM (rapid eye movement) sleep time and lower slow-wave activity during the NREM (non-rapid eye movement) sleep phase. These changes are also observed in obstructive sleep apnea (OSA). More severe OSA is correlated with lower levels of irisin and meteorin and higher levels of FGF-21 and interleukins 6 and 8. Conclusions: Taking into account the similarities in the myokine concentration changes in sarcopenia and in sleep disturbances, it may be concluded that alterations in the myokine levels induced by sarcopenia provoke sleep disturbances. However, it is necessary to further investigate these correlations to understand them better. Full article

Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or other rare tumors (1%). Given the high cure rates and the ability to histologically confirm tumor clearance, surgical therapy is the gold standard for the treatment of skin cancer. Conventional surgery is the most employed technique for the removal of non-melanoma skin cancer (NMSCs). Mohs Micrographic Surgery (MMS) is the most precise surgical method for the treatment of non-melanoma skin cancer, allowing for 100% margin evaluation, being the gold-standard method for surgical treatment of non-melanoma skin cancer. Whenever it is possible to obtain wide margins (4 to 6 mm), cure rates vary from 70% to 99%. Imiquimod, a synthetic imidazoquinolinone amine, is a topical immune response modifier approved by the U.S. Food and Drug Administration (FDA) for the treatment of external anogenital warts, actinic keratosis (AK), and superficial basal cell carcinoma (sBCC). The efficacy of imiquimod is primarily attributed to its ability to modulate both innate and adaptive immune responses, as well as its direct effects on cancer cells. Imiquimod exerts its immunomodulatory effects by activating Toll-like receptors 7 and 8 (TLR7/8) on various immune cells, including dendritic cells, macrophages, and natural killer (NK) cells. Upon binding to these receptors, imiquimod triggers the MyD88-dependent signaling pathway, leading to the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). This cascade leads to the production of pro-inflammatory cytokines, including interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). These cytokines enhance local inflammation, recruit additional immune cells to the tumor site, and stimulate antigen presentation, thereby promoting an anti-tumor immune response. Radiation therapy (RTh) may be employed as a primary treatment to BCC. It may also be employed as an adjuvant treatment to surgery for SCC and aggressive subtypes of BCC. RTh triggers both direct and indirect DNA damage on cancer cells and generates reactive oxygen species (ROS) within cells. ROS trigger oxidative damage to DNA, proteins, and lipids, exacerbating the cellular stress and contributing to tumor cell death. Recently, immunotherapy emerged as a revolutionary treatment for all stages of SCC. Cemiplimab is a human programmed cell death 1 (PD-1)-blocking antibody that triggers a response to over 50% of patients with locally advanced and metastatic SCC. A randomized clinical trial (RCT) published in 2022 revealed that cemiplimab was highly effective in the neoadjuvant treatment of large SCCs. The drug promoted a significant tumor size decrease, enabling organ-sparing operations and a much better cosmetic effect. A few months ago, a RCT of cemiplimab on adjuvant therapy for locally aggressive SCC was published. Interestingly, cemiplimab was administered to patients with local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features, revealed that cemiplimab led to much lower risks both of locoregional recurrence and distant recurrence. Full article

Background: SARS-CoV-2, originally described as a respiratory pathogen, has been identified as a multisystem disease with complex and interconnected pathophysiological processes. Methods: The PRISMA framework was used to systematically review the evidence and identify and synthesize it in PubMed, Scopus, and Web of Science databases between January 2020 and May 2025. Of the 1410 screened records, 161 peer-reviewed studies involving more than 2 million patients were included in the analysis. The frequency of organ involvement, important biomarkers, and long-term outcomes were derived, and the quality of the studies was assessed using standardized tools. Results: The quantitative synthesis showed that 78%, 32%, 43%, and 28% of hospitalized patients had pulmonary, cardiovascular, 43% neurological, and 28% renal issues, respectively, with 10–35% showing persistent organ dysfunction at 6 months post-infection. The most common were cytokine storm (IL-6 (Interleukin-6) > 100 pg/mL in 72% of severe cases), endothelial dysfunction (biomarkers elevated in 87% of patients), and microvascular thrombosis (D-dimer > 2000 ng/mL in 46% of patients). Most domains were scored as having moderate-to-high confidence in the quality assessment. Conclusions: COVID-19 has long-term, multi-organ sequelae that require integrated multidisciplinary management. Healthcare systems should be ready to participate in long-term monitoring, rehabilitation, and special therapeutic development. The results offer a strong evidence base for clinical practice and post-pandemic health policy. Full article

Background/Objectives: This systematic review aimed to gather the most recent evidence regarding the link between genetic polymorphisms and physical performance in team sports, with a focus on the practical utility of this information for athlete selection, training personalization, and injury prevention. Methods: Sixteen studies published between 2018 and 2025 were analyzed and selected from six international databases, in accordance with the PRISMA guideline. Only English-language studies were included, which evaluated active athletes in team sports and investigated associations between genetic variations, such as Actinin Alpha 3 (ACTN3 R577X), Angiotensin I Converting Enzyme (ACE I/D), Peroxisome Proliferator-Activated Receptor Alpha (PPARA), Interleukin 6 (IL6), and Nitric Oxide Synthase 3 (NOS3), and physical performance parameters. The methodological quality of the studies was assessed using the Q-Genie tool, with all studies scoring over 45 across all 11 items, indicating high quality. Results: The ACTN3 and ACE genes stood out due to their consistent association with traits such as strength, speed, endurance, and recovery capacity. Other genes, such as PPARA, Fatty Acid Amide Hydrolase (FAAH), Angiotensinogen (AGT), and NOS3, complemented this genetic profile by being involved in the regulation of energy metabolism and injury predisposition. An increasing number of studies have begun to adopt cumulative genotype scores, suggesting a shift from a monogenic approach to complex predictive models. Conclusions: The integration of genetic profiling into the evaluation and management of athletes in team sports is becoming increasingly relevant. Although current evidence supports the applicability of these markers, robust future research conducted under standardized conditions is necessary to validate their use in sports practice and to ensure sound ethical standards. Full article

Background: With a steady increase in prevalence, chronic obstructive pulmonary disease (COPD) is recognized as a leading contributor to global mortality, which underscores the need to identify prognostic biomarkers that are easy to use in everyday practice. As both local and systemic inflammation play a pivotal part in the development and progression of COPD, the purpose of our study was to assess the role of inflammatory markers in estimating disease severity (GOLD 1 to 4) to guide the management and treatment of patients with COPD, thus helping to reduce episodes of decompensation and fatal outcomes in both immediate and long-term contexts. Methods: We performed a descriptive observational analysis with a cross-sectional design including 100 patients with stable COPD. All subjects underwent standard clinical examination, lung function tests and a comprehensive inflammation blood panel. Results: We included 55 patients with mild–moderate COPD (GOLD 1–2), 33 patients with advanced stages of COPD (GOLD 3) and 12 patients with very severe forms of the disease (GOLD 4). Male sex, smoking status, BMI, IL-1 beta, NLR, and nocturnal heart rate were parameters with significant value for assessing COPD severity (p < 0.05 for all). NLR correlates significantly with the predicted distance in the 6 MWT (p = 0.039). Significant associations were identified between IL-8 and duration of exposure of biomass fuel (p = 0.045) as well as between IL-6 and pack-years (p = 0.024), with both prognostic and therapeutic impact. Furthermore, the analysis of the total cohort revealed positive correlations between serum IL-6 and FVC (%) (p = 0.033) or NLR and the ratio between FEV1 and FVC (p = 0.048). The neutrophil-to-lymphocyte ratio (NLR) proved to be a reliable indicator of stages 3–4 GOLD (AUC 0.66, threshold value 2.3045, p = 0.004—a one-point increase in NLR corresponded to a 2.148 increase in FEV1). Conclusions: NLR emerged as a simple, accessible and highly informative biomarker in COPD, linked to disease severity and functional decline. Its integration into routine assessment could enhance prognosis and guide clinical decisions, a finding that warrants confirmation in future multicenter studies. Full article