Serum IL-6 and IL-10 in Early Childhood Caries: A Sibling-Controlled Study in Children Aged 2.5-6 Years

Background: Early childhood caries (ECC) is a biofilm-mediated and sugar-driven disease associated with local and systemic inflammatory responses. This study evaluated serum Interleukin-6 (IL-6) and IL-10 concentrations, hematologic inflammatory indices, and oral inflammatory parameters in children with ECC compared with caries-free sibling controls. Methods: This sibling-controlled case-control study included 155 children aged 2.5-6 years, comprising 120 children with active ECC and 35 caries-free siblings. Serum IL-6 and IL-10 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Complete blood count parameters and derived inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), cumulative inflammatory index (IIC), and mean corpuscular volume-to-lymphocyte ratio (MCVL), were calculated. Plaque Index (PI) and Gingival Index (GI) were recorded in children with ECC. Group comparisons, correlation analyses, ROC analysis, and multivariable logistic regression were performed. Results: Children with ECC exhibited significantly higher serum IL-6 and IL-10 concentrations than sibling controls. MCVL values were significantly lower in the ECC group, whereas several inflammatory indices indicated an increased systemic inflammatory burden. Stratification by PI tertiles showed progressively higher values for WBC, NEU, NLR, SII, SIRI, AISI, and IIC as plaque accumulation increased (all p < 0.05). PI was strongly correlated with GI (r = 0.811, p < 0.001) and moderately correlated with NLR (r = 0.536), SII (r = 0.536), SIRI (r = 0.654), AISI (r = 0.648), and IIC (r = 0.546) (all p < 0.01). Serum IL-6 and IL-10 were strongly correlated (r = 0.804, p < 0.001) but not with PI or GI. ROC analysis demonstrated moderate discriminatory performance for IL-6 (AUC = 0.701) and IL-10 (AUC = 0.696). Age- and sex-adjusted multivariable logistic regression demonstrated that elevated IL-6 concentrations (adjusted OR = 1.36; 95% CI, 1.10-1.68; p = 0.005) remained independently associated with ECC, whereas increasing MCVL values (adjusted OR = 0.92; 95% CI, 0.86-0.98; p = 0.010) were associated with reduced odds of ECC. Conclusions: ECC is associated with systemic cytokine alterations and increased hematologic inflammatory burden. While IL-6 and IL-10 distinguish children with ECC from sibling controls, plaque accumulation severity is better reflected by composite hematologic inflammatory indices than by isolated cytokine concentrations. IL-6 and MCVL may be promising adjunctive biomarkers for ECC.