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1.
Altered stool cytokine profiles and pro-onflammatory/anti-inflammatory imbalance in children with autism spectrum disorder : a developmental analysis
Petra 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: 63; Downloads: 45
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2.
Unraveling the role of IL-17 in lichen planus : a comparative investigation of clinical variability and immunopathogenic pathways
Maja Tolušić Levak, Mirta Pauzar, Vera Plužarić, Nika Francesch, Biljana Pauzar, Jasmina Rajc, Marija Delaš Aždajić, Martina Mihalj, 2025, original scientific article

Abstract: Introduction: Lichen planus (LP) is a chronic T cell–mediated inflammatory disease affecting the skin and mucosa. Interleukin-17 (IL-17), a pro-inflammatory cytokine, has been implicated in LP pathogenesis, but its tissue-level expression across clinical variants remains underexplored. This study compares IL-17 expression in healthy skin and LP lesions and assesses variations based on clinical presentation. Methods: This cross-sectional retrospective study included 20 LP skin samples and 10 healthy controls. The sample collection spanned a period of 10 years. IL-17 expression was assessed via immunohistochemistry and quantified using a modified Q score. Samples were categorized by mucosal involvement and lesion distribution. Statistical analysis was performed with the MannWhitney U test. Results: IL-17 was absent in healthy skin but present in all LP samples. IL-17 expression was significantly higher in patients with both skin and oral mucosal involvement compared to those with cutaneous LP (p = 0.003). No significant difference was observed between generalized and localized LP. Conclusions: The results indicate a distinct increase in IL-17 expression in LP lesions, particularly with mucosal involvement, supporting its role in LP pathogenesis. These findings suggest IL-17 as a potential biomarker and therapeutic target, warranting further investigation in larger cohorts.
Keywords: inflammatory dermatoses, lichen planus, interleukin-17, immunoexpression
Published in DiRROS: 15.06.2026; Views: 268; Downloads: 195
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Effectiveness of oral glutathione in reducing nitric oxide and IL-1α concentrations for clinical improvement in mild to moderate acne vulgaris : a randomized controlled trial
Ferra Olivia Mawu, Anis Irawan Anwar, Khairuddin Djawad, Agussalim Bukhari, Marlyn Grace Kapantow, Paulus Mario Christopher, 2025, original scientific article

Abstract: Introduction: Acne vulgaris (AV) is a chronic inflammatory dermatosis predominantly affecting adolescents and young adults. Oxidative and nitrosative stress, marked by elevated nitric oxide (NO) and interleukin (IL)-1α, contributes to AV pathogenesis. Glutathione, a key antioxidant, may attenuate oxidative and nitrosative stress and modulate inflammatory pathways. This study investigates the effectiveness of oral glutathione supplementation on serum NO and IL-1α concentrations, and clinical improvement in mild to moderate AV patients. Methods: A randomized controlled trial was conducted involving 40 subjects diagnosed with mild to moderate AV. Participants were randomized to receive either 500 mg oral glutathione (n = 22) or placebo (n = 18) once daily for 4 weeks. Clinical severity of AV was assessed utilizing the Lehmann criteria. Serum levels of NO and IL-1α were measured at baseline and week 4. Results: At week 4, reductions in serum NO and IL-1α concentrations were observed in the glutathione group; however, these changes did not reach statistical significance (p > 0.05). Clinical improvement occurred in seven subjects (31.8%) in the glutathione group, with a reduction from moderate to mild severity. No adverse reactions were reported. Conclusions: Oral glutathione supplementation demonstrated a non-significant trend toward reducing oxidative and nitrosative stress markers and improving mild to moderate AV. Further studies are recommended to validate these findings.
Keywords: acne vulgaris, oxidative stress, nitric oxide, glutathione, interleukin-1α
Published in DiRROS: 15.06.2026; Views: 236; Downloads: 190
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IL-6 as an integrative biomarker of residual inflammation and visceral adiposity in psoriasis : a VAI threshold-dependent model
Eva Klara Merzel Šabović, Tadeja Kraner Šumenjak, Miodrag Janić, 2025, original scientific article

Abstract: Introduction: Psoriatic patients are frequently exposed to residual inflammation and visceral obesity, two factors that synergistically increase cardiometabolic risk. Methods: We evaluated IL-6 as a potential integrative biomarker linking these pathways in a cross-sectional study including 80 patients with well-controlled skin disease and 20 matched healthy controls. Serum IL-6 was measured by ELISA, and visceral adiposity estimated using the Visceral Adiposity Index (VAI). Results: Psoriatic patients displayed significantly higher IL-6 than controls (38.1 pg/mL [35.5–41.3] vs. 21.4 pg/mL [19.5–33.4]; p<0.001). A distinct VAI threshold of 1.3 was identified, above which IL-6 levels rose steeply until VAI 2.2 and then plateaued. Patients with VAI ≥1.3 had markedly higher IL-6 and pro-inflammatory cytokines than those below this cutoff. Random forest regression confirmed IFN-γ, IL-1β, IL-12p70, and IL-17 as dominant predictors of IL-6, while HbA1c, FIB-4, and treatment contributed minimally. Discussion: These findings suggest that IL-6 elevation in psoriasis primarily reflects cytokine-driven residual inflammation, with non-linear amplification once visceral adiposity exceeds a critical threshold. The threshold-dependent IL-6 dynamic highlights a clinically meaningful inflection point, integrating residual inflammation and visceral fat dysfunction, and may guide early cardiometabolic risk stratification and intervention. Prospective validation is warranted.
Keywords: interleukin-6, psoriasis, visceral adiposity index, systemic inflammation, obesity
Published in DiRROS: 23.03.2026; Views: 307; Downloads: 199
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7.
Prognostic impact of interleukin-27 in peripheral artery disease
Nataša Kokalj, Borut Jug, 2025, original scientific article

Abstract: Atherosclerosis is a progressive arterial disease characterized by chronic inflammation, with interleukin-27 (IL-27) implicated as both a pro- and anti-inflammatory cytokine. This prospective cohort study evaluated association of circulating IL-27 levels in peripheral artery disease patients undergoing elective endovascular revascularization, with major adverse cardiovascular events (MACE) and major adverse limb events (MALE) over a median follow-up of 311 days. Elevated IL-27 levels were significantly associated with increased risk of MACE and MALE in unadjusted analyses. After adjusting for established cardiovascular and PAD risk factors, IL-27 remained an independent predictor of MACE (HR 2.95; p = 0.039), but not MALE. These findings indicate that elevated IL-27 levels are associated with unfavourable long-term prognosis.
Keywords: peripheral artery disease, interleukin-27, endovascular revascularization, major adverse cardiovascular events, major adverse limb events
Published in DiRROS: 06.03.2026; Views: 429; Downloads: 306
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8.
Challenge of missing data in observational studies : investigating cross-sectional imputation methods for assessing disease activity in axial spondyloarthritis
Stylianos Georgiadis, Marion Pons, Simon Horskjær Rasmussen, Merete Lund Hetland, Louise Linde, Daniela Di Giuseppe, Brigitte Michelsen, Johan Karlsson Wallman, Tor Olofsson, Jakub Závada, Žiga Rotar, Katja Perdan-Pirkmajer, 2025, original scientific article

Abstract: Objectives: We aimed to compare various methods for imputing disease activity in longitudinally collected observational data of patients with axial spondyloarthritis (axSpA). Methods: We conducted a simulation study on data from 8583 axSpA patients from ten European registries. Disease activity was assessed by the Axial Spondyloarthritis Disease Activity Score (ASDAS) and the corresponding low disease activity (LDA; ASDAS<2.1) state at baseline, 6 and 12 months. We focused on cross-sectional methods which impute missing values of an individual at a particular time point based on the available information from other individuals at that time point. We applied nine single and five multiple imputation methods, covering mean, regression and hot deck methods. The performance of each imputation method was evaluated via relative bias and coverage of 95% confidence intervals for the mean ASDAS and the derived proportion of patients in LDA. Results: Hot deck imputation methods outperformed mean and regression methods, particularly when assessing LDA. Multiple imputation procedures provided better coverage than the corresponding single imputation ones. However, none of the evaluated methods produced unbiased estimates with adequate coverage across all time points, with performance for missing baseline data being worse than for missing follow-up data. Predictive mean and weighted predictive mean hot deck imputation procedures consistently provided results with low bias. Conclusions: This study contributes to the available methods for imputing disease activity in observational research. Hot deck imputation using predictive mean matching exhibited the highest robustness and is thus our suggested approach.
Keywords: axial spondyloarthritis, epidemiology, interleukin-17, tumour necrosis factor inhibitors
Published in DiRROS: 26.02.2026; Views: 429; Downloads: 258
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9.
Diagnosis, management, and monitoring of interleukin-1 mediated diseases in Central and Eastern Europe : real-world data
Marija Jelusic, Mario Sestan, Nataša Toplak, Tamas Constantin, Jelena Vojinović, Zbigniew Zuber, Beata Wolska-Kuśnierz, Mihaela Sparchez, Miloš Ješenák, Skirmante Rusoniene, 2025, original scientific article

Abstract: Background: Global healthcare disparities, stemming from organizational diferences in healthcare systems, lead to variable availability and funding, resulting in a gap between recommended and implemented practices for interleukin (IL)-1-mediated autoinfammatory diseases. We aimed to assess diagnostic, treatment and follow-up options for these diseases in Central and Eastern European countries, comparing them with the 2021 recommendations of the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR). Methods: In 2023, a structured collaborative efort was organized with representatives from 10 Central and Eastern European countries to address autoinfammatory diseases. The discussion focused on potential strategies to achieve the goals mentioned above. Results: Almost all the participating countries have specialized centers for the diagnosis and treatment of autoinfammatory diseases and the care is provided either by rheumatologists and/or clinical immunologists. Genetic testing is available in all countries, but there is variation in the types of tests ofered. Massive parallel sequencing panels for autoinfammatory diseases are available in all countries, with waiting periods for results ranging from 3 to 6 months in most cases. The availability of disease-specifc laboratory assessments, such as S100 proteins, is limited. IL-1 inhibitors are available in all countries, but there are diferences in practices regarding the licensing and reimbursement of anakinra and canakinumab based on specifc indications or diagnoses. The age at which the transition process begins varies, but in most countries, it typically starts around the age of 18 or beyond and in majority of the participating countries there is no structured transition program. Conclusions: Adherence to the 2021 EULAR/ACR recommendations for IL-1-mediated autoinfammatory diseases is achievable in Central and Eastern European countries. Determining the prevalence and incidence of these diseases in this region remains a persistent challenge for future research eforts, with the overarching goal of identifying new patients with autoinfammatory diseases.
Keywords: autoinfammatory diseases, interleukin-1 mediated diseases, diagnosis, treatment, monitoring, patientreported outcomes, transition
Published in DiRROS: 23.02.2026; Views: 540; Downloads: 294
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10.
Interleukin-6 extraction ratios during prolonged CytoSorb hemoadsorption depend on procedural blood flow
Jakob Gubenšek, Barbara Vajdič Trampuž, Matej Zrimšek, Vanja Peršič, 2025, original scientific article

Abstract: Background: Hemoadsorption with CytoSorb is a novel treatment for cytokine release syndrome, but there are few published data on the rate of cytokine removal with prolonged use. Here, we report a prospective observational study of IL-6 extraction ratios with prolonged CytoSorb use. Methods: A secondary analysis was conducted on a prospective observational cohort study involving patients treated with CytoSorb. Blood samples for IL-6 were taken before treatment, after 30 min, and every 6 h of treatment at three sites: (1) before the adsorber, (2) between the adsorber and dialyzer, and (3) after the dialyzer. The extraction ratios of the adsorber were then calculated. Results: We included 21 dialysis circuits performed in 15 critically ill patients, mainly those with cytokine storm because of septic shock. The median extraction ratio of IL-6 after 30 min was 26% (interquartile range, IQR 18-37%). The ratio decreased to 10% (6-21%) after 6 h and remained between 9-16% for up to 24 h (with a low number of circuits used beyond 12 h). Extraction ratios were similar in circuits with high (>1,000 ng/L) and low baseline IL-6 levels. On the contrary, in circuits with high blood flow (≥200 mL/min, i.e., intermittent hemodialysis), the extraction ratio was very low (median 6%) at 6 h and negligible thereafter, whereas the circuits with lower blood flow (<200 mL/min) maintained an extraction ratio of 20% for up to 12 h. Conclusion: We observed a significant reduction in the IL-6 extraction ratio within 6 h in circuits with high blood flow, whereas circuits with lower blood flow maintained an adequate extraction ratio for up to 12 h. Recent consensus recommendations on an 8-12 h exchange interval should mainly be applied to continuous dialysis methods, whereas in intermittent hemodialysis, the exchanges should be more frequent.
Keywords: CytoSorb, cytokines, hemoadsorption, interleukin 6 (IL6), reduction ratio, removal rate
Published in DiRROS: 13.01.2026; Views: 378; Downloads: 285
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