1. Stool mucosal immune protein–cytokine interconnections in children with autism spectrum disorder : an age-adjusted partial correlation analysisJoško Osredkar, Uroš Godnov, Maja Jekovec-Vrhovšek, Damjan Osredkar, Gorazd Avguštin, Teja Fabjan, Kristina Kumer, 2026, original scientific article Abstract: Children with autism spectrum disorder (ASD) exhibit gut mucosal immune alterations, but the co-regulatory architecture linking stool immune proteins and cytokines within the same cohort remains unstudied. In 115 children (74 ASD, 41 controls; age 5–18 years), seven stool immune proteins (IgA subclasses, α1-antitrypsin and calprotectin subunits) were quantified by UHPLC-MS/MS and ten by Luminex—chemokines eotaxin/CCL11 and IL-8/CXCL8 plus eight cytokines—each normalised to total protein. Age-adjusted partial Spearman correlations were computed for all 70 protein–cytokine pairs per stratum, using Benjamini–Hochberg correction, bootstrap confidence intervals and Fisher r-to-z tests. No pair survived FDR correction in any stratum. IgA1 and IL-1β/TP correlated positively across all strata (full cohort ρ = 0.409, 95% CI 0.131–0.634, n = 62; controls 0.583; ASD 0.210), with no significant between-group difference (Fisher z = 1.70, p = 0.090). Multiple imputation attenuated this to ρ = 0.265 (95% CI 0.055–0.452). An inverse trend between IL-1β/TP and CARS score (ρ = −0.336, n = 41) did not survive correction (p-FDR = 0.576). This power-limited, hypothesis-generating study identifies an exploratory IgA1–IL-1β mucosal axis present across groups, with no confirmed between-group difference. Adequately powered multi-centre studies are required.
Keywords: autism spectrum disorder, stool proteomics, cytokines, IgA, calprotectin, alpha-1-antitrypsin, IL-1β, gut mucosal immunity, partial Spearman correlation, Luminex
Published in DiRROS: 12.08.2026; Views: 92; Downloads: 54
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2. Altered stool cytokine profiles and pro-onflammatory/anti-inflammatory imbalance in children with autism spectrum disorder : a developmental analysisPetra Finderle, Maja Jekovec-Vrhovšek, Uršula Prosenc Zmrzljak, Damjan Osredkar, Gorazd Avguštin, Joško Osredkar, 2026, original scientific article Abstract: Background: Immune dysregulation and gut dysbiosis are increasingly implicated in autism spectrum disorder (ASD), but compartment-specific intestinal cytokine profiles remain poorly defined. Aim: To characterize stool cytokine profiles and pro-/anti-inflammatory balance in children with ASD across development. Methods: We analyzed stool samples from 283 children (109 controls, 104 mild ASD, 70 severe ASD; age 0.9–21.5 years) recruited at a tertiary centre. Nine cytokines (IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, TNF-α) were measured using a Luminex multi-plex assay; IL-15 was excluded due to >70% missing values. Group comparisons used Mann–Whitney U tests, with age stratification at the cohort median (≤9.5 vs. >9.5 years). A composite pro-/anti-inflammatory ratio (IL-1α + IL-1β + IL-6 + IL-8 + IL-17 + TNF-α + IFN-γ divided by IL-4 + IL-10) was calculated. Results: In the overall cohort, stool IL-8 and IL-4 were significantly decreased in ASD versus controls (IL-8: median 0.36 vs. 0.49 ng/L, p = 0.0041; IL-4: 0.28 vs. 0.30 ng/L, p = 0.0316), with a graded reduction from controls to mild and severe ASD. Age-stratified analysis revealed that IL-8 reduction was confined to younger children (≤9.5 years; p = 0.0025) and absent in older children, while IL-1β was significantly reduced in younger ASD children and tended to reverse in older ASD children. The pro-/anti-inflammatory ratio was markedly elevated in severe ASD (median 491 vs. 209 in controls; p = 0.059), particularly in older children. Stool IL-8 and IL-1β correlated inversely with CARS scores within the ASD group. Conclusions: Children with ASD show decreased stool IL-8 and IL-4 and a shift toward a pro-inflammatory cytokine balance, with the strongest alterations during early childhood. These findings are consistent with the hypothesis of a developmental window of intestinal immune dysregulation in ASD, with stool IL-8 as the primary FDR-corrected finding. The present cross-sectional data do not establish causality and independent replication is required before clinical conclusions are drawn.
Keywords: autism spectrum disorder, cytokines, stool biomarkers, IL-8, IL-4, interleukin, gut–immune axis, CARS, developmental immunology
Published in DiRROS: 06.08.2026; Views: 107; Downloads: 74
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3. Bronchopulmonary dysplasia and innate immunity : a narrative review of the roles of IL-1β and IL-8 (CXCL8)Dubravka Bačaj Ivanić, Štefan Grosek, Andreja Nataša Kopitar, 2026, review article Abstract: Background: Bronchopulmonary dysplasia (BPD) is a leading chronic lung complication in extremely premature newborns. The etiological factors contributing to of BPD include both prenatal and postnatal risk factors, as well as activation of innate immunity. Innate immunity and its bioactive mediators play a central role in orchestrating the inflammatory response. Among these, interleukin-1β (IL-1 β) and IL-8 (CXCL8) are particularly prominent. Methods: A structured literature search was conducted across major biomedical databases (PubMed, Scopus, Web of Science, and Ovid MEDLINE) to identify relevant studies published between 1993 and November 2025. Article selection was guided by predefined inclusion criteria focusing on studies that examined IL-1β and IL-8 (CXCL8) in relation to bronchopulmonary dysplasia. Evidence from both human and animal studies was narratively synthesized. Results: This review provides a detailed description of the role of the innate immune system in BPD, including mechanisms of inflammatory initiation, evidence from human and animal studies on IL-1β and IL-8 (CXCL8), and the interaction between these two cytokines in the development of chronic lung disease. Conclusions: Both human and animal studies generally suggest that elevated levels of IL-1β and IL-8 (CXCL8) are closely associated with the development of bronchopulmonary dysplasia in premature infants.
Keywords: premature infant, chronic lung disease, inflammation, cytokines, chemokines
Published in DiRROS: 22.07.2026; Views: 181; Downloads: 92
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4. Detection of serum and tissue levels of interleukin 39 in psoriasis : a case control studyMohammed Hassan, Talal A. Abd El-Raheem, Olfat G. Shake, Hagar Ali Kamal, Sara M. Yaseen, Amira E. Soliman, 2025, original scientific article Abstract: Introduction: Psoriasis is a chronic immune-mediated disorder with a genetic component that primarily affects the skin and has potential systemic involvement. Advances in understanding the interaction between the innate and adaptive immune systems have facilitated improved disease management. Methods: This study included 25 patients with psoriasis and 20 healthy controls of both sexes. All participants underwent detailed medical history-taking and dermatological examination, including assessment of the body surface area and the Psoriasis Area and Severity Index (PASI). Blood samples (3 ml) were collected from all subjects, and 4 mm lesional skin punch biopsies were obtained from psoriatic patients and healthy controls. Results: Serum and tissue levels of interleukin 39 (IL-39) were significantly elevated in psoriatic patients compared to healthy individuals. Patients with a positive family history of psoriasis showed higher serum IL-39 levels than those without such a history. In addition, psoriatic individuals with diabetes mellitus or hypertension had higher serum IL-39 levels than those without these comorbidities. A statistically significant correlation was found between disease severity and serum IL-39 concentration. Conclusions: Elevated serum and tissue IL-39 levels in psoriatic patients suggest a potential role for IL-39 in the pathogenesis of psoriasis, highlighting its possible utility as a biomarker or therapeutic target.
Keywords: psoriasis, cytokines, autoimmune disease, IL-39, ELISA
Published in DiRROS: 15.06.2026; Views: 257; Downloads: 168
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5. Glioblastoma–natural killer cell crosstalk: insights from dynamic spheroid models reveal the importance of secreted cytokines and the CD155 axisAnamarija Habič, Tina Kolenc Milavec, Pia Žižek, Špela Kladnik, Bernarda Majc, Emanuela Senjor, Milica Perišić, Andrej Porčnik, Borut Prestor, Urban Švajger, Metka Novak, Barbara Breznik Vittori, 2026, original scientific article Abstract: Glioblastoma (GB) is an aggressive primary brain cancer with poor patient prognosis. Natural killer (NK) cells can recognise and eliminate a range of malignant cells, including GB stem cells, which drive GB recurrence. NK cell-based immunotherapy has emerged as a promising approach for GB treatment, but a better understanding of the complex crosstalk between GB and NK cells is needed, particularly within the immunosuppressive GB tumour microenvironment. In this study, we established a reproducible protocol for the production and dynamic culture of uniformly sized GB spheroids using the Celvivo Clinostar system. Our spheroids recapitulated the heterogeneous structure of GB and expressed ligands for NK cell receptors at levels distinct from those observed in corresponding GB cell lines in standard culture, implicating altered sensitivity of GB cells to NK cells in dynamic 3D cultures. GB-NK cell crosstalk was GB cell type dependent and the ability of NK cells to infiltrate GB did not necessarily correlate with their cytotoxicity against GB cells. Spheroids derived from differentiated GB cells secreted higher levels of immunomodulatory cytokines compared to spheroids from GB stem-like cells, and a prominent increase in the secretion of immune-attracting factors was observed in their co-cultures with NK cells. Finally, the CD155-DNAM1/TIGIT axis was indicated as an important regulator of NK cell cytotoxicity against GB stem-like cells. Collectively, our results highlight important factors in GB-NK cell communication and provide a groundwork for further targeted research as well as therapeutic evaluation of NK cell-based approaches in the established dynamic 3D cultures.
Keywords: glioblastoma, immunotherapy, dynamic in vitro models, natural killer cells, cytotoxicity, 21 infiltration, cytokines, CD155
Published in DiRROS: 11.06.2026; Views: 272; Downloads: 233
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6. Joint inflammation correlates with joint GPR30 expression in males and hippocampal gpr30 expression in females in a rat model of rheumatoid arthritisTanja Grubić-Kezele, Hrvoje Omrčen, Lara Batičić, Sandra Šućurović, Sanja Zoričić Cvek, 2024, original scientific article Abstract: Abstract: It is not entirely clear how the interaction between joint inflammation and the central nervous system (CNS) response in rheumatoid arthritis (RA) works, and what pathophysiology underlies the sex differences in coexisting neuropsychiatric comorbidities. It is known that estrogen hormones reduce inflammation in RA and that this occurs mainly via the stimulation of G protein-coupled receptor-30 (GPR30), also known as G protein-coupled estrogen receptor (GPER) 1. However, changes in GPR30 expression and sex differences induced by local and systemic inflammation in RA are not yet known. Our aim was to reveal sex differences in the expression and association of joint GPR30 with local and systemic inflammation, clinical course and furthermore with hippocampal GPR30 expression during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Furthermore, we demonstrated sex-specific differences in the association between joint and systemic inflammation and hippocampal microglia during PIA. Our results suggest sex-specific differences not only in the clinical course and serum levels of pro-inflammatory cytokines but also in the expression of GPR30. Female rats show greater synovial inflammation and greater damage to the articular cartilage compared to males during PIA attack. Male rats express higher levels of synovial and cartilaginous GPR30 than females during PIA, which correlates with a less severe clinical course. The correlation between synovial and cartilaginous GPR30 and joint inflammation scores (Krenn and Mankin) in male rats suggests that the more severe the joint inflammation, the higher the GPR30 expression. At the same time, there is no particular upregulation of hippocampal GPR30 in males. On the other hand, female rats express higher levels of neuroprotective GPR30 in the hippocampus than male rats at the basic level and during PIA attack. In addition, females have a higher number of Iba-1+ cells in the hippocampus during PIA attack that strongly correlates with the clinical score, serum levels of IL-17A, and Krenn and Mankin scores. These results suggest that male rats are better protected from inflammation in the joints and female rats are better protected from the inflammation in the hippocampus during a PIA attack, independently of microglia proliferation. However, in the remission phase, synovial GPR30 expression suddenly increases in female rats, as does hippocampal GPR30 expression in males. Further experiments with a longer remission period are needed to investigate the molecular background of these sex differences, as well as microglia phenotype profiling
Keywords: cytokines, G protein-coupled estrogen receptor 1, hippocampus
Published in DiRROS: 10.06.2026; Views: 194; Downloads: 168
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7. Dynamics of serum levels of TNF-α in a longitudinal follow-up study in 98 patients with juvenile idiopathic arthritis treated with anti-TNF-α biological drugsNataliia Morozova, Mojca Zajc Avramovič, Gašper Markelj, Nataša Toplak, Tadej Avčin, 2024, original scientific article Abstract: Objective: To determine the dynamics of serum levels of TNF-α in patients with juvenile idiopathic arthritis (JIA) treated with anti-TNF-α biological drugs and investigate their association with the disease activity. Methods: We conducted a single-centre, observational cohort study in 98 patients with JIA (30 boys, 68 girls, mean age 11.3 years) treated with anti-TNF-α biological drugs. Clinical examinations and laboratory assessments of serum levels of TNF-α were performed before starting therapy with biological drug and at 6-month intervals afterwards up to 2.5 years. Results: The analysis of serum levels of TNF-α in relation to the disease activity states showed the highest mean serum levels of TNF-α in patients on etanercept who had low disease activity states and in patients on adalimumab who had inactive disease. The correlation analysis in patients with JIA treated with etanercept or adalimumab showed a weak negative correlation between the serum levels of TNF-α and JADAS10 scores (p = 0.007), (r = - 0.177). Conclusion: The assessment of serum levels of TNF-α in children with JIA during treatment with etanercept or adalimumab is not a reliable biomarker of disease activity or immunological remission. Longitudinal measurement of TNF-α has no added clinical value in patients with JIA treated with anti-TNF-α biological drugs. Key Points • There is limited evidence regarding the effect of anti-TNF therapy on serum concentrations of TNF-α in patients with juvenile idiopathic arthritis • Our study showed an increase in the serum level of TNF-α after the initiation of therapy with either etanercept or adalimumab, which was more significant in patients with inactive or low disease activity • Serum TNF-α is most likely not biologically active during therapy with TNF-α inhibitors and therefore not a reliable biomarker of disease activity or immunological remission in patients with juvenile idiopathic arthritis
Keywords: adalimumab, cytokines, etanercept, juvenile idiopathic arthritis, tumour necrosis factor-alpha
Published in DiRROS: 05.06.2026; Views: 267; Downloads: 102
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8. Increased frequency of circulating activated FOXP3+ regulatory T cell subset in patients with chronic lymphocytic leukemia is associated with the estimate of the size of the tumor mass, STAT5 signaling and disease course during follow-up of patients on therapyZlatko Roškar, Mojca Dreisinger, Evgenija Homšak, Tadej Avčin, Sebastjan Bevc, Aleš Goropevšek, 2024, original scientific article Keywords: chronic lymphocytic leukemia, signal transduction, cytokines, T cells
Published in DiRROS: 04.06.2026; Views: 266; Downloads: 183
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9. Degenerative disease of intervertebral disc : a narrative review of pathogenesis, clinical implications and therapiesLidija Gradišnik, Nina Kočivnik, Uroš Maver, Tomaž Velnar, 2026, review article Abstract: This narrative review examines degenerative disc disease (DDD), a major cause of chronic back pain and disability worldwide. It is a multifactorial condition resulting from a complex interplay of genetic, mechanical, metabolic, and environmental factors that progressively impair disc structure and function. The pathophysiology of DDD involves disruption of extracellular matrix homeostasis, cellular senescence, oxidative stress, and chronic inflammation mediated by cytokines such as IL-1β, TNF-α, and IL-6. These processes are further modulated by signalling pathways including NF-κB, MAPK, and Wnt/β-catenin, leading to matrix degradation, dehydration, and loss of disc height. Epidemiological studies highlight the contribution of lifestyle and metabolic disorders, such as obesity, smoking, and diabetes, to disease progression. Traditional conservative and surgical treatments primarily alleviate symptoms but do not halt or reverse degeneration. In contrast, recent advances in molecular biology and regenerative medicine have opened new therapeutic avenues. Mesenchymal stem cell therapy, biomaterial scaffolds, and gene-based interventions aim to restore disc homeostasis by promoting matrix synthesis and suppressing catabolic activity. Despite promising experimental results, clinical translation remains limited by challenges in cell viability, delivery methods, and long-term efficacy. Future research integrating molecular, biomechanical, and regenerative strategies offers the potential for true biological repair and disc regeneration.
Keywords: intervertebral disc, degenerative disc disease, oxidative stress, cytokines, cellular senescence
Published in DiRROS: 08.04.2026; Views: 323; Downloads: 259
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10. The role of cytokines and chemokines as biomarkers of disease activity in idiopathic nephrotic syndrome in childrenMatjaž Kopač, Aleš Jerin, Agnese Petrera, Joško Osredkar, 2025, original scientific article Abstract: This study investigates the association of plasma concentrations of various cytokines and chemokines with the disease activity of idiopathic nephrotic syndrome (INS) in children in Slovenia. (2) In a prospective single-center study lasting 18 months, we took sequential plasma samples from children with INS at disease onset or relapse (prior to corticosteroid (CS) therapy), at remission, and after discontinuation of CS therapy. The Olink®Target 48 Cytokine Panel was applied to analyze 45 analytes in the plasma samples, adhering to the manufacturer’s protocol. We performed a statistical analysis with a paired samples analysis with a t-test as well as with a non-parametric Wilcoxon correction test. (3) We included 18 pediatric patients with INS in the study. We demonstrated statistically significant differences in the concentrations of CSF1, IL4, FLT3LG, CCL19, and MMP12 in the patients at disease onset or relapse compared to those in remission, differences in the concentrations of CSF1 and IL17F in the patients at disease onset or relapse compared to those in remission after CS treatment, and differences in the concentrations of CCL19, MMP12, and CCL13 in the patients in remission compared to those in remission after CS treatment. (4) The findings support potential roles of certain cytokines and chemokines, especially CSF1, CCL19, and MMP12, in influencing the disease activity of INS.
Keywords: cytokines, chemokines, idiopathic nephrotic syndrome, children
Published in DiRROS: 12.02.2026; Views: 652; Downloads: 275
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