Interleukins (IL-1β, IL-4, IL-6, and IL-8) in Aqueous Humor as Potential Biomarkers of Diabetic Retinopathy Severity
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Bogomolets National Medical University, Kyiv, Ukraine
Publication date: 2025-11-30
Wiadomości Lekarskie 2025;(11):2251-2262
KEYWORDS
ABSTRACT
Aims: To determine the concentrations of interleukins (IL1ß, IL4, IL6, IL8) in the aqueous humor and their association with diabetic retinop
athy
severity.
Materials and Methods: Singlecenter crosssectional study with prospective sampling of 110 adults with type 2 diabetes mellitus spanning five categories of
diabetic retinopathy and 25 nondiabetic controls. Aqueous humor (0.1 mL) obtained during phacoemulsification was analyzed by ELISA. Nonparametric tests
assessed group differences; optimal thresholds were derived by multiclass onevsall ROC-analysis, followed by clinically relevant binary stratification (mild/
moderate vs severe DR). Spearman rank correlations evaluated relationships with age, diabetes duration, fasting glucose, HbA1c, and Cpeptide.
Results: All interleukins differed between groups (p < 0.001). IL1ß and IL6 increased with stage; IL8 peaked at severe nonproliferative disease and declined in
proliferative disease; IL4 decreased. Multiclass accuracies were modest: 56%, 58%, 53%, and 44% for IL-6, IL8, IL1ß, and IL4. In the binary model, IL6 achieved
72.6% accuracy (95% CI 64.3-79.9), with cutoffs of 34.4-86.2 and >86.2 pg/mL for mild/moderate and severe disease. IL8 was supportive (62.2%; severe
>216.9 pg/mL). IL1ß and IL4 each yielded about 55.6%. Correlations were weak to moderate: IL6 and IL8 tracked diabetes duration and glycemia, while IL4
inversely tracked Cpeptide.
Conclusions: IL6 is the most informative single local biomarker for binary severity stratification of diabetic retinopathy, with IL8 as an adjunct and IL1ß/ IL4 of
limited standalone value. IL6 thresholds may guide riskadapted followup and monitoring with optical coherence tomography and optical coherence tomography
angiography. External validation, preanalytical standardization, and prospective outcome studies are needed.