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BMC Oral Health
Published in: BMC Oral Health 1/2023

Open Access 01-12-2023 | Cytokines | Research

Positive correlational shift between crevicular antimicrobial peptide LL-37, pain and periodontal status following non-surgical periodontal therapy. A pilot study

Authors: David Madruga, Miguel M Garcia, Luca Martino, Haidar Hassan, Ghada Elayat, Lucy Ghali, Laura Ceballos

Published in: BMC Oral Health | Issue 1/2023

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Abstract

Background

Periodontitis has a high prevalence and uncertain recurrence. Unlike the pro-inflammatory cytokine profile, little is known about the anti-inflammatory cytokine and antimicrobial peptide overview following treatment. The present study aimed to evaluate if any of the antimicrobial peptide LL-37, interleukin (IL) 4, 10 and 6 together with the volume of gingival crevicular fluid (GCF) and total protein concentration in GCF could be used as correlative biomarkers for the severity in periodontitis as well as prognostic factors in the management of the disease.

Methods

Forty-five participants were recruited and allocated to the healthy (15), Stage I-II (15) or Stage III-IV periodontitis (15) group. Along with periodontal examination, GCF samples were obtained at baseline and 4–6 weeks following scaling and root planing (SRP) for the periodontitis groups. GCF samples were analyzed by ELISA kits to quantify LL-37 and IL-4, -6 and − 10. One-way ANOVA followed by Dunnett’s test was used to determine differences among the three groups at baseline. Two-way ANOVA followed by Sidak’s post-hoc test was used to compare between pre- and post-SRP in the two periodontitis groups.

Results

The amount of GCF volume was significantly correlated to the severity of periodontitis and decreased following SRP, particularly in the Stage III-IV group (p < 0.01). The levels of LL-37, IL-6, and pain and periodontal clinical parameters were significantly correlated to the severity of periodontitis. IL-4 and IL-10 in the periodontitis groups were significantly lower than the healthy group (p < 0.0001) and barely improved following SRP up to the level of the healthy group.

Conclusions

With the limitations of this study, crevicular LL-37 may be a candidate for a biomarker of periodontitis and the associated pain upon probing.

Trial registration

The study was registered in clinical trials.gov, with number NCT04404335, dated 27/05/2020.
Appendix
Available only for authorised users
Literature
1.
Varma SR, Thomas B, Ramesh A, Kumari S, Shahira MA, Saadi ZA, et al. Estimation of sialic acid and IL10 levels in stage 1 and 2 periodontitis patients. Int J Dent. 2019;2019:2917124.PubMedPubMedCentralCrossRef
2.
3.
Bamashmous S, Kotsakis GA, Jain S, Chang AM, McLean JS, Darveau RP. Clinically healthy human gingival tissues show significant inter-individual variability in GCF chemokine expression and subgingival plaque microbial composition. Front Oral Health. 2021;12:689475.CrossRef
4.
Moutsopoulos NM, Konkel JE. Tissue-specific immunity at the oral mucosal barrier. Trends Immunol. 2018;39(4):276–87.PubMedCrossRef
5.
Su Y, Gao J, Kaur P, Wang Z. Neutrophils and macrophages as targets for development of nanotherapeutics in inflammatory diseases. Pharmaceutics. 2020;12(12):1222.PubMedPubMedCentralCrossRef
6.
7.
Garcia MM, Goicoechea C, Molina-Álvarez M, Pascual D. Toll-like receptor 4: a promising crossroads in the diagnosis and treatment of several pathologies. Eur J Pharmacol. 2020;874:172975.PubMedCrossRef
8.
Doss M, White MR, Tecle T, Hartshorn KL. Human defensins and LL-37 in mucosal immunity. J Leukoc Biol. 2010;87(1):79–92.PubMedCrossRef
9.
Wang C, Wang S, Li D, Chen P, Han S, Zhao G, et al. Human cathelicidin inhibits SARS-CoV-2 infection: killing two birds with one stone. ACS Infect Dis. 2021;7(6):1545–54.PubMedCrossRef
10.
Puklo M, Guentsch A, Hiemstra PS, Eick S, Potempa J. Analysis of neutrophil-derived antimicrobial peptides in gingival crevicular fluid suggests importance of cathelicidin LL-37 in the innate immune response against periodontogenic bacteria. Oral Microbiol Immunol. 2008;23(4):328–35.PubMedPubMedCentralCrossRef
11.
Yang D, Chen Q, Chertov O, Oppenheim JJ. Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol. 2000;68(1):9–14.PubMedCrossRef
12.
Pütsep K, Carlsson G, Boman HG, Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet. 2002;360(9340):1144–9.PubMedCrossRef
13.
Carlsson G, Wahlin YB, Johansson A, Olsson A, Eriksson T, Claesson R, et al. Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia. J Periodontol. 2006;77(4):744–51.PubMedCrossRef
14.
Turkoglu O, Emingul G, Eren G, Atmaca H, Kutukculer N, Atilla G. Levels of LL-37 antimicrobial peptide in the gingival crevicular fluid of young and middle-aged subjects with or without gingivitis. J Istanb Univ Fac Dent. 2017;51(1):15–21.PubMedPubMedCentral
15.
Jia W, Schults AJ, Jensen MM, Ye X, Alt JA, Prestwich GD, Oottamasathien S. Bladder pain in an LL-37 interstitial cystitis and painful bladder syndrome model. Am J Clin Exp Urol. 2017;5(2):10–7.PubMedPubMedCentral
16.
Vernal R, Dutzan N, Chaparro A, Puente J, Antonieta Valenzuela M, Gamonal J. Levels of interleukin-17 in gingival crevicular fluid and in supernatants of cellular cultures of gingival tissue from patients with chronic periodontitis. J Clin Periodontol. 2005;32:383–9.PubMedCrossRef
17.
Sánchez-Hernández PE, Zamora-Perez AL, Fuentes-Lerma M, Robles-Gómez C, Mariaud-Schmidt RP, Guerrero-Velázquez C. IL-12 and IL-18 levels in serum and gingival tissue in aggressive and chronic periodontitis. Oral Dis. 2011;17(5):522–9.PubMedCrossRef
18.
Papathanasiou E, Teles F, Griffin T, Arguello E, Finkelman M, Hanley J, Theoharides TC. Gingival crevicular fluid levels of interferon-γ, but not interleukin-4 or -33 or thymic stromal lymphopoietin, are increased in inflamed sites in patients with periodontal disease. J Periodontal Res. 2014;49(1):55–61.PubMedCrossRef
19.
Miranda TS, Figueiredo NF, Figueiredo LC, Silva HDPD, Rocha FRG, Duarte PM. Cytokine profiles of healthy and diseased sites in individuals with periodontitis. Arch Oral Biol. 2020;120:104957.PubMedCrossRef
20.
Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011;1813(5):878–88.PubMedCrossRef
21.
Al-Hamoudi N, Alsahhaf A, Al Deeb M, Alrabiah M, Vohra F, Abduljabbar T. Effect of scaling and root planing on the expression of anti-inflammatory cytokines (IL-4, IL-9, IL-10, and IL-13) in the gingival crevicular fluid of electronic cigarette users and non-smokers with moderate chronic periodontitis. J Periodontal Implant Sci. 2020;50(2):74–82.PubMedPubMedCentralCrossRef
22.
Napimoga MH, Nunes LH, Maciel AA, Demasi AP, Benatti BB, Santos VR, Bastos MF, de Miranda TS, Duarte PM. Possible involvement of IL-21 and IL-10 on salivary IgA levels in chronic periodontitis subjects. Scand J Immunol. 2011;74(6):596–602.PubMedCrossRef
23.
Archana A, Sasireka S, Prabhu MN, Bobby B, Srikanth V. Correlation between circulatory and salivary IL-10 levels in periodontal helath and disease –a report. Int J Dent Sci Res. 2014;2(4B):7–10.CrossRef
24.
25.
Liu Y, Zhang C, Wu J, Yu H, Xie C. Evaluation of the relationship among dental fear, scaling and root planing and periodontal status using periodontitis stages: a retrospective study. J Dent Sci. 2022;17(1):293–9.PubMedCrossRef
26.
Sanz I, Alonso B, Carasol M, Herrera D, Sanz M. Nonsurgical treatment of periodontitis. J Evid Based Dent Pract. 2012;12(3 Suppl):76–86.PubMedCrossRef
27.
Stein JM, Yekta-Michael SS, Schittenhelm F, Reichert S, Kupietz D, Dommisch H, et al. Comparison of three full-mouth concepts for the non-surgical treatment of stage III and IV periodontitis: a randomized controlled trial. J Clin Periodontol. 2021;48(12):1516–27.PubMedCrossRef
28.
Danser MM, van Winkelhoff AJ, de Graaff J, Loos BG, van der Velden U. Short-term effect of full-mouth extraction on periodontal pathogens colonizing the oral mucous membranes. J Clin Periodontol. 1994;21(7):484–9.PubMedCrossRef
29.
Petersilka GJ, Ehmke B, Flemmig TF. Antimicrobial effects of mechanical debridement. Periodontol 2000. 2002;28:56–71.PubMedCrossRef
30.
Caton JG. A new classification scheme for periodontal and peri-implant diseases and conditions –introduction and key changes from the 1999 classification. J Clin Periodontol. 2018;45(Suppl 20):1–S8.
31.
Grant MM, Taylor JJ, Jaedicke K, Creese A, Gowland C, Burke B, Doudin K, Patel U, Weston P, Milward M, Bissett SM, Cooper HJ, Kooijman G, Rmaile A, de Jager M, Preshaw PM, Chapple ILC. Discovery, validation, and diagnostic ability of multiple protein-based biomarkers in saliva and gingival crevicular fluid to distinguish between health and periodontal diseases. J Clin Periodontol. 2022;49(7):622–32.PubMedPubMedCentralCrossRef
32.
Löe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol. 1967;38(6):uppl.CrossRef
33.
Tsze DS, von Baeyer CL, Pahalyants V, Dayan PS. Validity and reliability of the verbal numerical rating scale for children aged 4 to 17 years with acute pain. Ann Emerg Med. 2018;71(6):691–702e3.PubMedCrossRef
34.
Guentsch A, Kramesberger M, Sroka A, Pfister W, Potempa J, Eick S. Comparison of gingival crevicular fluid sampling methods in patients with severe chronic periodontitis. J Periodontol. 2011;82(7):1051–60.PubMedPubMedCentralCrossRef
35.
Lowenguth RA, Greenstein G. Clinical and microbiological response to nonsurgical mechanical periodontal therapy. Periodontol 2000. 1995;9:14–22.PubMedCrossRef
36.
37.
Nazir MA. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int J Health Sci (Qassim). 2017;11(2):72–80.PubMed
38.
Atarbashi-Moghadam F, Talebi M, Mohammadi F, Sijanivandi S. Recurrence of periodontitis and associated factors in previously treated periodontitis patients without maintenance follow-up. J Adv Periodontol Implant Dent. 2020;12(2):79–83.PubMedPubMedCentralCrossRef
39.
Leow NM, Moreno F, Marletta D, Hussain SB, Buti J, Almond N, et al. Recurrence and progression of periodontitis and methods of management in long-term care: a systematic review and meta-analysis. J Clin Periodontol. 2022;49(Suppl 24):291–313.PubMedCrossRef
40.
Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004;361(1–3):184–7.PubMedCrossRef
41.
42.
Vanderwall AG, Milligan ED. Cytokines in pain: harnessing endogenous anti-inflammatory signaling for improved pain management. Front Immunol. 2019;10:3009.PubMedPubMedCentralCrossRef
43.
Majeed ZN, Philip K, Alabsi AM, Pushparajan S, Swaminathan D. Identification of gingival crevicular fluid sampling, analytical methods, and oral biomarkers for the diagnosis and monitoring of periodontal diseases: a systematic review. Dis Markers. 2016;2016:1804727.
44.
Ghallab NA. Diagnostic potential and future directions of biomarkers in gingival crevicular fluid and saliva of periodontal diseases: review of the current evidence. Arch Oral Biol. 2018;87:115–24.PubMedCrossRef
45.
Fatima T, Khurshid Z, Rehman A, Imran E, Srivastava KC, Shrivastava D. Gingival crevicular fluid (GCF): a diagnostic tool for the detection of periodontal health and diseases. Molecules. 2021;26(5):1208.PubMedCrossRef
46.
Pradeep AR, Roopa Y, Swati PP. Interleukin-4, a T-helper 2 cell cytokine, is associated with the remission of periodontal disease. J Periodontal Res. 2008;43:712–6.PubMedCrossRef
47.
Tokajuk J, Deptuła P, Piktel E, Daniluk T, Chmielewska S, Wollny T, et al. Cathelicidin LL-37 in health and diseases of the oral cavity. Biomedicines. 2022;10(5):1086.PubMedPubMedCentralCrossRef
48.
Elsadek MF, Ahmed BM, Eskandrani RM. Level of pain intensity, cytokine profiling and microbial load after photodynamic therapy in acute severe pericoronitis. Photodiagnosis Photodyn Ther. 2020;31:101830.PubMedCrossRef
Metadata
Title
Positive correlational shift between crevicular antimicrobial peptide LL-37, pain and periodontal status following non-surgical periodontal therapy. A pilot study
Authors
David Madruga
Miguel M Garcia
Luca Martino
Haidar Hassan
Ghada Elayat
Lucy Ghali
Laura Ceballos
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-023-03023-w

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