Inflammatory Biomarkers in Irreversible Pulpitis and Pulp Necrosis: A Systematic Review and Meta-Analysis

Accurate differentiation between irreversible pulpitis (IP) and pulp necrosis (PN) is crucial for clinical treatment planning, yet meta-analyses comparing their inflammatory biomarkers are lacking. Isolated findings limit the identification of consistent biomarker patterns, hindering diagnostic accuracy and stage-specific treatment development.

This systematic review and meta-analysis aimed to compare expression levels of inflammatory biomarkers in permanent teeth diagnosed with IP or PN vs healthy pulp, to elucidate disease-specific molecular profiles.

Electronic searches were performed in PubMed, Scopus, and Cochrane databases for studies published from inception to 2024. Eligible studies included human permanent teeth with IP or PN and reported quantitative protein-based biomarker levels. Forty-three studies met the inclusion criteria, with 26 included in the meta-analysis. Data were pooled using random-effects models, and standardized mean differences were calculated.

Symptomatic IP (SIP) showed significantly elevated TNF-α, IL-2, IL-6, IL-8, Substance P, CGRP, and catalase compared to healthy pulp. Asymptomatic IP (AIP) also exhibited significantly increased TNF-α despite the absence of clinical symptoms. No significant difference in TNF-α was observed between SIP and AIP. High heterogeneity was observed due to variation in sample types, analytical methods, and diagnostic criteria. Although a meta-analysis for PN was not feasible, descriptive analysis revealed consistently elevated TNF-α, IFN-γ, IL-10, and TGF-β levels in pulp necrosis.

Both SIP and AIP exhibit pro-inflammatory profiles, with TNF-α elevated regardless of symptoms. Molecular biomarkers may better reflect pulp status than clinical signs.

Elevated TNF-α levels observed in SIP and AIP indicate the presence of underlying inflammatory activity even in the absence of clinical symptoms. This finding highlights its potential value in helping to determine the appropriate window for vital pulp therapy.