Cytokine Changes in Gingival Crevicular Fluid and Serum After Non-Surgical Periodontal Therapy in Patients with Periodontitis: A Systematic Review and Narrative Synthesis.

Objective: We aimed to synthesize paired pre/post human evidence on how Th17-axis cytokines (IL-17A, IL-21, IL-22, IL-23 and related markers) change after non-surgical periodontal therapy (NSPT) by biospecimen (gingival crevicular fluid [GCF], saliva, serum) and time window. Material and methods: We performed a PRISMA-guided systematic review of non-randomized pre/post cohorts and clinical trials. Databases (PubMed, Embase, Scopus, Cochrane) were searched; two reviewers performed selection, data extraction, ROBINS-I risk-of-bias appraisal, and GRADE certainty assessment. Due to heterogeneity in sampling/assays and incomplete variance reporting, a qualitative direction-of-effect synthesis was prespecified for ≤4 weeks, ~6-8 weeks, and ~3-6 months. Results: Twelve studies (total n = 897) met inclusion (8 GCF; 5 blood-derived (serum/plasma) cohorts; one saliva). Most GCF cohorts reported decreases in IL-17A within ~6-8 weeks post-NSPT (≥4 cohorts), with one early 4-week cohort showing a concentration increase but an unchanged total amount due to reduced GCF volume. IL-23 generally declined locally and declined by ~3 months systemically in aggressive periodontitis. Serum IL-17A changes were smaller/variable (two cohorts reported decreases within 1-6 months), and one cohort showed a reduced IL-17A:IL-17E ratio at ~25 weeks. Heterogeneity precluded meta-analysis; we undertook a direction-of-effect synthesis. Conclusions: NSPT is likely associated with the early local down-regulation of Th17-axis activity (notably GCF IL-17A), when systemic signals are smaller and delayed. Given moderate-serious risk of bias and pre-analytical heterogeneity, the certainty of evidence is low to very low; Th17-axis biomarkers are not yet suitable for clinical decision-making.