Systemic effects of experimental apical periodontitis in animal models: Does lesion burden modulate circulating inflammatory and metabolic responses? A systematic review and meta-analysis

Objective This systematic review and meta-analysis evaluated whether experimental apical periodontitis (AP) in rodents induces systemic inflammatory and metabolic alterations and whether lesion burden influences these responses. Design The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and was registered in PROSPERO. PubMed/MEDLINE, EMBASE, Web of Science, and LILACS/BIREME were searched through June 2026. Experimental rodent studies with AP induction, condition-matched controls without AP, and quantitative systemic biomarkers were included. Primary outcomes were circulating inflammatory cytokines; secondary outcomes included glycemic, insulin-related, and lipid parameters. Hedges’ g was pooled using multilevel random-effects models, with effect sizes nested within studies. Meta-regression assessed lesion burden, experimental duration, comorbidity, and animal model when sufficient data were available. Results: Thirty studies were included in the synthesis. AP was associated with higher circulating tumor necrosis factor-α (g = 1.69), interleukin (IL)-6 (g = 0.96), and IL-1β (g = 1.84), whereas IL-10, IL-17, and IL-18 were not significantly altered. AP was also associated with higher insulin (g = 1.19) and homeostatic model assessment for insulin resistance (HOMA-IR) (g = 1.55), but not with glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides. Lesion burden did not significantly moderate the inflammatory or metabolic outcomes. Conclusions The number of lesions did not significantly modify the magnitude of the systemic responses evaluated. Experimental AP was associated with selective alterations, including increased TNF-α, IL-6, IL-1β, insulin, and HOMA-IR. Among the moderators analyzed, only animal model influenced the IL-6 response, although this finding was exploratory.