Non-Cochrane · aetiology · PM41747365
Inflammatory Biomarkers in Irreversible Pulpitis and Pulp Necrosis: A Systematic Review and Meta-Analysis.
Wahyudi Rahman, Aguilar Panuroot, Changsiripun Chidsanu, et al. · International dental journal · 2026 · PubMed · doi:10.1016/j.identj.2026.109453
Findings
23 findings
| Population | ||||
|---|---|---|---|---|
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | IL-8 level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -1.86 [-2.42, -1.3] Low Downgraded: risk of bias, inconsistency, publication bias 6 studies · 243 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | CGRP level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -2.4 [-3.41, -1.38] Low Downgraded: risk of bias, imprecision, inconsistency, publication bias 7 studies · 222 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | Catalase level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -1.41 [-2.35, -0.46] Low Downgraded: risk of bias, imprecision, inconsistency 3 studies · 113 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | TNF-α level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -2.08 [-3.46, -0.7] Low Downgraded: risk of bias, inconsistency 5 studies · 194 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | Substance P level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Assay method: Radioimmunoassay | SMD -2.87 [-5.73, -0.01] GRADE not reported 3 studies · 102 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | IL-6 level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Assay method: ELISA | SMD -7.42 [-18.28, 3.43] GRADE not reported 2 studies · 61 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | CGRP level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Assay method: Radioreceptor assay | SMD -2.17 [-4.11, -0.23] GRADE not reported 2 studies · 18 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | MMP-9 level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Assay method: Fluorometric assay | SMD -2.0 [-3.48, -0.51] GRADE not reported 2 studies · 82 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | IL-2 level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -1.61 [-3.14, -0.08] Low Downgraded: risk of bias, imprecision, inconsistency 4 studies · 169 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | IL-2 level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Sensitivity analysis: excluding studies with median/IQR converted to mean/SD | SMD -1.54 [-3.62, 0.55] GRADE not reported 3 studies · 122 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | IL-8 level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Sensitivity analysis: excluding studies with median/IQR converted to mean/SD | SMD -1.9 [-4.13, 0.34] GRADE not reported 2 studies · 65 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | IL-8 level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Assay method: ELISA | SMD -1.96 [-2.89, -1.02] GRADE not reported 4 studies · 142 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | IL-6 level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -2.75 [-4.82, -0.68] Low Downgraded: risk of bias, imprecision, inconsistency 3 studies · 122 participants |
| Human permanent teeth (pulp-derived samples) | Symptomatic irreversible pulpitis (SIP) | Healthy pulp | IL-8 level Single time point (biomarker level at diagnosis/sampling) · Pulp tissue, pulpal blood or other pulp-derived samples · Assay method subgroup analysis: all studies in the subgroup plot (ELISA and CBA) | SMD -1.95 [-2.64, -1.26] GRADE not reported 5 studies · 203 participants |
| Human permanent teeth (pulp-derived samples) | Symptomatic irreversible pulpitis (SIP) | Healthy pulp | CGRP level Single time point (biomarker level at diagnosis/sampling) · Pulp tissue, pulpal blood or other pulp-derived samples · Assay method subgroup analysis: all studies in the subgroup plot (ratio data) | SMD -1.39 [-1.87, -0.9] GRADE not reported 7 studies · 222 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | Substance P level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -3.16 [-5.54, -0.78] Low Downgraded: risk of bias, inconsistency 4 studies · 127 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | Catalase level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Assay method: Spectrophotometric | SMD -1.84 [-2.42, -1.26] GRADE not reported 2 studies · 71 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | CGRP level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Assay method: Flow cytometry | SMD -1.07 [-1.74, -0.4] GRADE not reported 3 studies · 104 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | MMP-9 level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -1.27 [-2.85, 0.31] Low Downgraded: risk of bias, imprecision, inconsistency 3 studies · 124 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | TNF-α level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Assay method: ELISA | SMD -2.6 [-3.95, -1.25] GRADE not reported 4 studies · 159 participants |
| Permanent teeth with symptomatic irreversible pulpitis (SIP) | Symptomatic irreversible pulpitis (exposure) | Healthy pulp | TNF-α level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth · Sensitivity analysis: excluding studies with median/IQR converted to mean/SD | SMD -3.71 [-7.07, -0.35] GRADE not reported 2 studies · 82 participants |
| Permanent teeth with asymptomatic irreversible pulpitis (AIP) | Asymptomatic irreversible pulpitis (exposure) | Healthy pulp | TNF-α level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -1.41 [-2.82, 0.0] Low Downgraded: risk of bias, imprecision, inconsistency 3 studies · 133 participants |
| Permanent teeth with irreversible pulpitis | Asymptomatic irreversible pulpitis (AIP) | Symptomatic irreversible pulpitis (SIP) | TNF-α level in dental pulp Pulp samples (tissue, pulpal blood, exudate) from human permanent teeth | SMD -0.19 [-1.45, 1.06] GRADE not reported 3 studies · 163 participants |
Included primary studies 79
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Awawdeh, Lundy 2002 Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth. PMID:11853236 | 2002 | 1 other review | not stated | not extracted yet |
| Bowles 2003 Tissue levels of immunoreactive substance P are increased in patients with irreversible pulpitis. PMID:12701777 | 2003 | 1 other review | not stated | not extracted yet |
| Castillo-Silva 2019 Expression of calcitonin gene-related peptide and pulp sensitivity tests in irreversible pulpitis. PMID:31531564 | 2019 | 1 other review | not stated | not extracted yet |
| Caviedes-Bucheli 2004 Expression of calcitonin gene-related peptide (CGRP) in irreversible acute pulpitis. PMID:15085045 | 2004 | 1 other review | not stated | not extracted yet |
| Caviedes-Bucheli 2005 Calcitonin gene-related peptide receptor expression in healthy and inflamed human pulp tissue. PMID:16164685 | 2005 | 1 other review | not stated | not extracted yet |
| Caviedes-Bucheli 2006 Quantification of neuropeptides (calcitonin gene-related peptide, substance P, neurokinin A, neuropeptide Y and vasoactive intestinal… PMID:16640639 | 2006 | 1 other review | not stated | not extracted yet |
| Caviedes-Bucheli 2008 Calcitonin gene-related peptide receptor expression in alternatively activated monocytes/macrophages during irreversible pulpitis. PMID:18634925 | 2008 | 1 other review | not stated | not extracted yet |
| Jain 2024 matched by author and year (probable) | NR | 1 other review | not stated | not extracted yet |
| Sattari 2010 Substance P and CGRP expression in dental pulps with irreversible pulpitis. PMID:20666750 | 2010 | 1 other review | not stated | not extracted yet |
| Sharma 2021 matched by author and year (probable) | NR | 1 other review | MMP-9 level in dental pulp | not extracted yet |
| Abd-Elmegui 2013 Osteocalcin expression in pulp inflammation. PMID:23791253 | 2013 | this review only | not stated | not extracted yet |
| Abd-Elmeguid 2013 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Abouelenien 2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Abouelenien 2024 Cytokine expression of IL-8 before and after root canal treatment in patients with symptomatic apical periodontitis: A clinical trial. PMID:37818971 | 2024 | this review only | not stated | not extracted yet |
| Accorsi-Mendonça 2013 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Accorsi-Mendonça 2013 Evaluation of gelatinases, tissue inhibitor of matrix metalloproteinase-2, and myeloperoxidase protein in healthy and inflamed human… PMID:23791255 | 2013 | this review only | not stated | not extracted yet |
| Akbal Dincer 2020 matched by author and year (probable) | NR | this review only | IL-8 level | not extracted yet |
| Anderson 2002 matched by author and year (probable) | NR | this review only | IL-2 level in dental pulp | not extracted yet |
| Anderson 2002 Evaluating IL-2 levels in human pulp tissue. PMID:12236309 | 2002 | this review only | not stated | not extracted yet |
| Awawdeh 2002 matched by author and year (probable) | NR | this review only | Substance P level in dental pulp; CGRP level in dental pulp | not extracted yet |
| Awawdeh 2002 (PGE2) matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Ayoub 2017 matched by author and year (probable) | NR | this review only | TNF-α level in dental pulp | not extracted yet |
| Ayoub 2017 Comparison of IL-1β, TNF-α, hBD-2, and hBD-3 Expression in the Dental Pulp of Smokers Versus Nonsmokers. PMID:29033092 | 2017 | this review only | not stated | not extracted yet |
| Barkhordar 1999 matched by author and year (probable) | NR | this review only | IL-6 level in dental pulp | not extracted yet |
| Barkhordar 1999 Detection of interleukin-6 in human dental pulp and periapical lesions. PMID:10219150 | 1999 | this review only | not stated | not extracted yet |
| Bowles 2003 matched by author and year (probable) | NR | this review only | Substance P level in dental pulp | not extracted yet |
| Castillo-Silva 2019 matched by author and year (probable) | NR | this review only | CGRP level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2004 matched by author and year (probable) | NR | this review only | CGRP level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2005 matched by author and year (probable) | NR | this review only | CGRP level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2006 matched by author and year (probable) | NR | this review only | Substance P level in dental pulp; CGRP level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2008 matched by author and year (probable) | NR | this review only | CGRP level in dental pulp | not extracted yet |
| ElSalhy 2013 matched by author and year (probable) | NR | this review only | TNF-α level in dental pulp; IL-2 level in dental pulp; IL-6 level in dental pulp; IL-8 level | not extracted yet |
| ElSalhy 2013 Cytokines as diagnostic markers of pulpal inflammation. PMID:23240887 | 2013 | this review only | not stated | not extracted yet |
| Esposito 2003 matched by author and year (probable) | NR | this review only | Catalase level in dental pulp | not extracted yet |
| Esposito 2003 Catalase activity in human healthy and inflamed dental pulps. PMID:12950573 | 2003 | this review only | not stated | not extracted yet |
| Golbasi 2022 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Golbasi 2022 Comparison of ADAMTS Levels in Pulp Tissue Samples of Healthy and Symptomatic Irreversible Pulpitis Teeth. PMID:34914940 | 2022 | this review only | not stated | not extracted yet |
| Gresser 2015 Methyl mercaptan and hydrogen sulfide products stimulate proinflammatory cytokines in patients with necrotic pulp tissue and… PMID:25864743 | 2015 | this review only | not stated | not extracted yet |
| Gulzar 2021 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Halkai 2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Huang 1999 matched by author and year (probable) | NR | this review only | IL-8 level | not extracted yet |
| Huang 1999 Increased interleukin-8 expression in inflamed human dental pulps. PMID:10468466 | 1999 | this review only | not stated | not extracted yet |
| Isett 2003 matched by author and year (probable) | NR | this review only | IL-8 level | not extracted yet |
| Isett 2003 Effect of an intraosseous injection of depo-medrol on pulpal concentrations of PGE2 and IL-8 in untreated irreversible pulpitis. PMID:12701778 | 2003 | this review only | not stated | not extracted yet |
| Jacobi-Gresser 2015 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Jain S 2024 Comparision of interleukin-1β concentrations in posttreatment endodontic disease and other pulpal and periapical conditions - A clinical… PMID:39372575 | 2024 | this review only | not stated | not extracted yet |
| Karapanou 2008 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Karapanou 2008 Interleukin-8 is increased in gingival crevicular fluid from patients with acute pulpitis. PMID:18215670 | 2008 | this review only | not stated | not extracted yet |
| Kritikou 2021 matched by author and year (probable) | NR | this review only | TNF-α level in dental pulp; IL-2 level in dental pulp; Catalase level in dental pulp; MMP-9 level in dental pulp | not extracted yet |
| Lepinski 2000 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Lepinski 2000 Bradykinin levels in dental pulp by microdialysis. PMID:11471646 | 2000 | this review only | not stated | not extracted yet |
| Li 2022 Correlation between Transforming Growth Factor-β and Periapical Lesions in Patients with Chronic Apical Periodontitis. PMID:35360476 | 2022 | this review only | not stated | not extracted yet |
| Mente 2016 matched by author and year (probable) | NR | this review only | MMP-9 level in dental pulp | not extracted yet |
| Mente 2016 A Prospective Clinical Pilot Study on the Level of Matrix Metalloproteinase-9 in Dental Pulpal Blood as a Marker for the State of… PMID:26725178 | 2016 | this review only | not stated | not extracted yet |
| Nakanishi 1995 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Nakanishi 1995 Quantitative analysis of immunoglobulins and inflammatory factors in human pulpal blood from exposed pulps. PMID:7561655 | 1995 | this review only | not stated | not extracted yet |
| Nawal 2024 matched by author and year (probable) | NR | this review only | TNF-α level in dental pulp; IL-8 level | not extracted yet |
| Nawal 2024 Discriminatory performance of the pulpal inflammatory biomarkers; Interleukin-8 and TNF-α in patients with symptoms indicative of… PMID:38703070 | 2024 | this review only | not stated | not extracted yet |
| Pezelj-Ribaric 2002 matched by author and year (probable) | NR | this review only | TNF-α level in dental pulp | not extracted yet |
| Pezelj-Ribaric 2002 Detection of tumor necrosis factor alpha in normal and inflamed human dental pulps. PMID:12459320 | 2002 | this review only | not stated | not extracted yet |
| Proctor 1991 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Proctor 1991 Determination and relationship of C-reactive protein in human dental pulps and in serum. PMID:1940751 | 1991 | this review only | not stated | not extracted yet |
| Rauschenberger 1997 matched by author and year (probable) | NR | this review only | IL-2 level in dental pulp | not extracted yet |
| Rauschenberger 1997 Detection of human IL-2 in normal and inflamed dental pulps. PMID:9545944 | 1997 | this review only | not stated | not extracted yet |
| Sabeti 2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Sabeti M.A. 2024 Expression of Selected Inflammatory Mediators with Different Clinical Characteristics of Pulpal Inflammation. PMID:38147909 | 2024 | this review only | not stated | not extracted yet |
| Sattari 2010 matched by author and year (probable) | NR | this review only | Substance P level in dental pulp; CGRP level in dental pulp | not extracted yet |
| Sharma 2021 Association between concentration of active MMP-9 in pulpal blood and pulpotomy outcome in permanent mature teeth with irreversible… PMID:33128238 | 2021 | this review only | not stated | not extracted yet |
| Soliman 2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Soliman A.A. 2024 Influence of Diclofenac Potassium versus Prednisolone on Postendodontic Pain and Pulpal Interleukin-8 Expression in Symptomatic… PMID:38925367 | 2024 | this review only | not stated | not extracted yet |
| Spoto 2001 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Spoto 2001 Aspartate aminotransferase activity in human healthy and inflamed dental pulps. PMID:11487132 | 2001 | this review only | not stated | not extracted yet |
| Toledo 2019 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Toledo 2019 Cytokines and chemokines associated with Treg/Th17 response in chronic inflammatory periapical disease. PMID:31664358 | 2019 | this review only | not stated | not extracted yet |
| Topçu 2016 matched by author and year (probable) | NR | this review only | Catalase level in dental pulp | not extracted yet |
| Topçu 2016 Catalase activity in healthy and inflamed pulp tissues of permanent teeth in young people. PMID:27538547 | 2016 | this review only | not stated | not extracted yet |
| Varvara 2005 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Varvara 2005 Copper-zinc superoxide dismutase activity in healthy and inflamed human dental pulp. PMID:15743423 | 2005 | this review only | not stated | not extracted yet |
| Wu 2022 The detection of pro-inflammatory cytokines in exudates from dental pulp tissues. PMID:35255379 | 2022 | this review only | not stated | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Permanent teeth | Human permanent teeth (n=8 to 104 participants per study; 43 studies) |
| Intervention | Irreversible pulpitis and pulp necrosis (exposure) | Symptomatic irreversible pulpitis (SIP), asymptomatic irreversible pulpitis (AIP); pulp necrosis only described narratively |
| Comparison | Healthy pulp (control group) | Healthy pulp; SIP as comparator for AIP |
| Outcomes | Protein inflammatory biomarker levels in dental pulp | TNF-α, IL-2, IL-6, IL-8, Substance P, CGRP, catalase, MMP-9 (SIP vs healthy pulp, k=3 to 7); TNF-α (AIP vs healthy pulp, k=3; AIP vs SIP, k=3) |
| Study designs | Randomized controlled trials and cross-sectional studies | Cross-sectional studies (38) and RCTs (5) |
| Timing | Not specified | Not specified |