Cytokine profile of saliva in adults with focal enamel demineralization after orthodontic treatment
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Abstract
Background and aim
the saliva content and correlation with the intensity of caries of proinflammatory cytokines IL-1ß, IL-6, IL-8 and anti-inflammatory cytokines IL-4 and IL-10 were studied in patients with FED after long-term orthodontic treatment.
Materials and methods
26 patients aged 18 to 30 years were divided into three groups: a group of patients without caries, a group with compensated caries with a caries intensity index (DMF decayed, missing, filled) value of less than 5.0 and a group with decompensated caries with a caries intensity index value of more than 5.0.
Results
based on the results obtained, it was found that patients with FED have violations both in the system of nonspecific and specific local immunity, which is more pronounced in patients with decompensated caries. The essential role of the proinflammatory cytokine IL-6 was noted, the content of which in saliva significantly prevails in patients with decompensated caries.
Conclusion
the study of the correlation relationships of the studied cytokines allowed us to determine the significant role of IL-6 and IL-4 cytokines and their ratios in the pathogenesis of FED.
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This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/18728652.
Summary of main findings and contribution
This preprint reports a small observational study measuring salivary cytokines (IL‑1β, IL‑6, IL‑8, IL‑4, IL‑10) in adults after long-term fixed orthodontic treatment. The authors report lower IL‑8 and IL‑4 in the FED groups and emphasize a higher IL‑6 (and altered IL‑6/IL‑4 and IL‑6/IL‑10 ratios) in the decompensated-caries subgroup, interpreting these as immune dysregulation relevant to FED pathogenesis.
Major issues
Core design confounding (FED vs caries vs orthodontic exposure): The study question is framed around FED after orthodontic treatment, but the groups are essentially stratified by caries intensity, and the comparison group is …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/18728652.
Summary of main findings and contribution
This preprint reports a small observational study measuring salivary cytokines (IL‑1β, IL‑6, IL‑8, IL‑4, IL‑10) in adults after long-term fixed orthodontic treatment. The authors report lower IL‑8 and IL‑4 in the FED groups and emphasize a higher IL‑6 (and altered IL‑6/IL‑4 and IL‑6/IL‑10 ratios) in the decompensated-caries subgroup, interpreting these as immune dysregulation relevant to FED pathogenesis.
Major issues
Core design confounding (FED vs caries vs orthodontic exposure): The study question is framed around FED after orthodontic treatment, but the groups are essentially stratified by caries intensity, and the comparison group is "practically healthy" without caries (and not clearly matched on orthodontic exposure), making it hard to attribute cytokine differences specifically to FED rather than to caries status and/or other differences between recruited populations.
Inconsistencies/ambiguity in group definitions and sample counts: The abstract states 26 patients divided into three groups including "patients without caries," yet the Methods state 26 orthodontic-treated participants, FED diagnosed in 24, with two FED subgroups (n=10, n=14) plus a separate comparison group (n=10), which is internally confusing and affects interpretability of results and denominators.
Minor issues
Summary statistics vs nonparametric testing: The paper reports means ± (SD/SE) while using Mann–Whitney tests; the authors can consider reporting medians and IQR and provide effect sizes with confidence intervals for group differences.
Evidence appraisal
Overall strength of evidence is limited for claims about "key roles" of IL‑6/IL‑4 in FED pathogenesis, because the design is cross-sectional, small (FED subgroups n=10 and n=14), and strongly confounded by caries status and likely other unmeasured factors. Although the results are consistent with between-group differences in some cytokines/ratios in this specific sample, but causal or mechanistic inferences about FED are not well supported without better controls and more rigorous statistical control for multiplicity and confounding.
Recommendations for improvement
Clarify the scientific contrast: Redesign or reframe analyses to cleanly separate effects of (a) FED presence/severity, (b) orthodontic exposure, and (c) caries intensity; at minimum add a bracket-treated group without FED and/or match controls on orthodontic history.
Strengthen reporting to STROBE: Add setting/recruitment dates, participant flow (screened/eligible/included/analyzed), missing-data counts per variable, and clearly prespecified objectives and primary endpoints.
Add confounder measurement: Collect/report oral hygiene indices, dietary sugar frequency, gingival/periodontal inflammation measures, smoking status, medication use, and time since debonding.
Competing interests
The author declares that they have no competing interests.
Use of Artificial Intelligence (AI)
The author declares that they did not use generative AI to come up with new ideas for their review.
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