Immune-inflammatory Modulation by Non-surgical Therapies in Peri-implantitis
Abstract
To evaluate the effects of non-surgical treatment on inflammatory factor levels in patients with peri-implantitis (PI).
PubMed, Web of Science, ScienceDirect, China National Knowledge Infrastructure, and Wanfang were searched through March 2026 for randomized controlled trials of non-surgical therapy for PI. Outcomes included interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and matrix metalloproteinase 8 (MMP-8). Meta-analysis was performed using RevMan 5.3.
Fourteen trials were included. At 3 months, adjunctive non-surgical treatment produced greater reductions than control treatment in gingival crevicular fluid IL-1β (SMD, −0.78; 95% CI, −1.29 to −0.26), IL-6 (SMD, −1.49; 95% CI, −2.07 to −0.91), and TNF-α (SMD, −1.84; 95% CI, −3.05 to −0.63), but not MMP-8 (SMD, 0.08; 95% CI, −1.33 to 1.50). At 6 months, no between-group difference was observed for IL-1β (SMD, −0.18; 95% CI, −0.61 to 0.25). PDT-based regimens reduced IL-1β and TNF-α more than controls at 3 months, whereas laser-based regimens showed no clear advantage. Non-smokers showed greater IL-1β improvement than smokers. Sensitivity analyses supported the IL-1β, IL-6, and TNF-α findings, but the MMP-8 result was unstable. GRADE evidence quality was moderate for IL-1β, IL-6, and TNF-α and low for MMP-8.
Non-surgical treatment may reduce gingival crevicular fluid IL-1β, IL-6, and TNF-α levels in the short term. Non-smokers may respond better than smokers, and PDT-based regimens may be more effective than laser therapy; however, benefits were not sustained at 6 months.
1. Chen L, Tong Z, Luo H. Titanium particles in peri-implantitis: distribution, pathogenesis, and prospects. Int J Oral Sci. 2023;15(1):49.
2. Cui Z, Wang P, Gao W. Microbial dysbiosis in periodontitis and peri-implantitis: pathogenesis, immune responses, and therapeutic. Front Cell Infect Mi. 2025;15:1517154.
3. Berglundh T, Mombelli A, Schwarz F. Etiology, pathogenesis, and treatment of peri-implantitis: a European perspective. Periodontol 2000. 2024:10–1111.
4. Smeets R, Henningsen A, Jung O, Heiland M, Hammächer C, Stein JM. Definition, etiology, prevention, and treatment of peri-implantitis: a review. Head Face Med. 2014;10:34.
5. Bassetti M, Schär D, Wicki B, et al; Anti-infective therapy of peri-implantitis with adjunctive local drug delivery or
photodynamic therapy: 12-month outcomes of a randomized controlled clinical trial. Clin Oral Implan Res. 2014;25(3):279–87.
6. Fornel DG, Ferrisse TM, de Oliveira AB, Fontana CR. Photodynamic therapy can modulate the nasopharyngeal carcinoma microenvironment infected with the Epstein-Barr virus: a systematic review and meta-analysis. Biomedicines. 2023;11(5):1344.
7. Ahmed AR, Kamran MA, Suleman G, Sharif RA, Alamrey AAM, Sulaiman SA. Novel use of chloro-aluminum phthalocyanine-assisted photodynamic therapy helps in periimplant healing among smoking patients. Photodiagn Photodyn Ther. 2023;41:103193.
8. Al-Khureif AA, Mohamed BA, Siddiqui AZ. Clinical, host-derived immune biomarker, and microbiological outcomes with adjunctive photochemotherapy compared with local antimicrobial therapy in the treatment of peri-implantitis in cigarette smokers. Photodiagn Photodyn Ther. 2020;30:101684.
9. Altindal D, Alkan EA, Calisir M. Evaluation of the effectiveness of diode laser therapy in conjunction with nonsurgical treatment of peri-implantitis. J Periodontal Implan. 2023;53(5):376–87.
10. Erduran NE, Guncu GN, Akman AC, et al; Evaluation of the effect of adjunctive diode laser application on peri-implant crevicular fluid biomarker levels: a randomized controlled trial. Clin Oral Invest. 2024;28(8):459.
11. Nedumaran N, Rajasekar A. Impact of rose bengal-mediated antimicrobial photodynamic therapy adjunctive to mechanical debridement on clinical, microbiological, and immunological parameters in peri-implantitis: a parallel, single-blinded, randomized controlled trial. Laser Med Sci. 2025;40(1):300.
12. Chambrone L, Wang HL, Romanos GE. Non-surgical mechanical therapy of peri-implantitis with or without repeated adjunctive diode laser application: a 6-month double-blinded randomized clinical trial. Clin Oral Implan Res. 2022;33(9):900–12.
13. Reyila Ai-ke-lan-mu, Reanguli A-bu-du-wei-li, Guo T, et al; Application effect and microbial ecological reconstruction analysis of probiotic regulation combined with photodynamic therapy in peri-implantitis. J North Sichuan Med Coll. 2025;40(8):991–6.
14. Hu MN, Sun F, Zhou YH. Clinical and microbiological effects of Lactobacillus reuteri as adjuvant therapy for peri-implantitis. Chin J Microecol. 2019;31(8):934–9.
15. Li SN, Song W. Effect of semiconductor laser on treatment of mild-to-moderate periimplantitis. Chin J Nosocomiol. 2023;33(13):2032–6.
16. Liu Y, Fan ZH, Yang CHSH. Short-term effect of implant grinding and polishing combined with drugs and laser therapy on peri-implantitis. J Mod Stomatol. 2023;37(6):401–6.
17. Liu XX, Ma X, Yang SY. Efficacy of photodynamic therapy as an adjunct in the treatment of peri-implantitis. Acta Univ Med Anhui. 2018;53(4):645–8.
18. Tian XM, Liu YQ, Li L, et al; Clinical study on joint application of Er,Cr:YSGG laser and implant polishing in treating peri-implantitis. Chin J Laser Med Surg. 2023;32(6):306–12.
19. Zhao YJ, Li RH, Ren G, et al; Effect of low-level laser treatment combined with initial periodontal therapy on IL-8, b-FGF, and IL-1β content in gingival crevicular fluid in peri-implantitis. Int J Biomed Eng. 2019;42(2):130–3.
20. Soysal F, Unsal B, Isler SC, Akca G, Bakirarar B, Ozcan M. Evaluation of salivary stress markers and inflammatory cytokine levels in patients with peri-implantitis. Clin Oral Invest. 2024;28(5):290.
21. Chmielewski M, Pilloni A. Current molecular, cellular, and genetic aspects of peri-implantitis disease: a narrative review. Dent J-Basel. 2023;11(5):134.
22. Guarnieri R, Reda R, Di Nardo D, et al; Expression of IL-1β, IL-6, TNF-α, and a-MMP-8 in sites with healthy conditions and with periodontal and peri-implant diseases: a case-control study. J Dent Res Dent Clin Dent Prospects. 2024;18(2):135–42.
23. Nart J, Pons R, Valles C, Esmatges A, Sanz-Martín I, Monje A. Non-surgical therapeutic outcomes of peri-implantitis: 12-month results. Clin Oral Invest. 2020;24(2):675–82.
24. Elsadek MF. Effectiveness of 2 photosensitizer-mediated photodynamic therapies for treating moderate peri-implant infections in patients with type 2 diabetes mellitus: a randomized clinical trial. Photodiagn Photodyn Ther. 2023;43:103643.
25. Almoharib H. Erbium-doped yttrium aluminum garnet (Er:YAG) lasers in the treatment of peri-implantitis. Cureus J Med Science. 2025;17(1):e78279.
26. Chen JH, Lin YC, Kung JC, et al; Efficacy of Er:YAG laser for peri-implantitis treatment and microbiological changes: a randomized controlled trial. Laser Med Sci. 2022;37(9):3517–25.
27. Świder K, Dominiak M, Grzech-Leśniak K, Matys J. Effect of different laser wavelengths on periodontopathogens in peri-implantitis: a review of in vivo studies. Microorganisms. 2019;7(7):189.
28. Neophytou C, Vlachodimou E, Kaklamanos EG, Sakellari D, Papadimitriou K. Microbiological effects of laser-assisted non-surgical treatment of peri-implantitis: a systematic review and meta-analysis of randomized controlled trials. Dent J-Basel. 2026;14(1):49.
29. Sun D, Li Z, Li D, Wu B, Ma Y. Laser combined with mechanical debridement enhances pain relief and inflammation control in the management of periodontitis with peri-implantitis. Am J Transl Res. 2025;17(7):5698–5709.
2. Cui Z, Wang P, Gao W. Microbial dysbiosis in periodontitis and peri-implantitis: pathogenesis, immune responses, and therapeutic. Front Cell Infect Mi. 2025;15:1517154.
3. Berglundh T, Mombelli A, Schwarz F. Etiology, pathogenesis, and treatment of peri-implantitis: a European perspective. Periodontol 2000. 2024:10–1111.
4. Smeets R, Henningsen A, Jung O, Heiland M, Hammächer C, Stein JM. Definition, etiology, prevention, and treatment of peri-implantitis: a review. Head Face Med. 2014;10:34.
5. Bassetti M, Schär D, Wicki B, et al; Anti-infective therapy of peri-implantitis with adjunctive local drug delivery or
photodynamic therapy: 12-month outcomes of a randomized controlled clinical trial. Clin Oral Implan Res. 2014;25(3):279–87.
6. Fornel DG, Ferrisse TM, de Oliveira AB, Fontana CR. Photodynamic therapy can modulate the nasopharyngeal carcinoma microenvironment infected with the Epstein-Barr virus: a systematic review and meta-analysis. Biomedicines. 2023;11(5):1344.
7. Ahmed AR, Kamran MA, Suleman G, Sharif RA, Alamrey AAM, Sulaiman SA. Novel use of chloro-aluminum phthalocyanine-assisted photodynamic therapy helps in periimplant healing among smoking patients. Photodiagn Photodyn Ther. 2023;41:103193.
8. Al-Khureif AA, Mohamed BA, Siddiqui AZ. Clinical, host-derived immune biomarker, and microbiological outcomes with adjunctive photochemotherapy compared with local antimicrobial therapy in the treatment of peri-implantitis in cigarette smokers. Photodiagn Photodyn Ther. 2020;30:101684.
9. Altindal D, Alkan EA, Calisir M. Evaluation of the effectiveness of diode laser therapy in conjunction with nonsurgical treatment of peri-implantitis. J Periodontal Implan. 2023;53(5):376–87.
10. Erduran NE, Guncu GN, Akman AC, et al; Evaluation of the effect of adjunctive diode laser application on peri-implant crevicular fluid biomarker levels: a randomized controlled trial. Clin Oral Invest. 2024;28(8):459.
11. Nedumaran N, Rajasekar A. Impact of rose bengal-mediated antimicrobial photodynamic therapy adjunctive to mechanical debridement on clinical, microbiological, and immunological parameters in peri-implantitis: a parallel, single-blinded, randomized controlled trial. Laser Med Sci. 2025;40(1):300.
12. Chambrone L, Wang HL, Romanos GE. Non-surgical mechanical therapy of peri-implantitis with or without repeated adjunctive diode laser application: a 6-month double-blinded randomized clinical trial. Clin Oral Implan Res. 2022;33(9):900–12.
13. Reyila Ai-ke-lan-mu, Reanguli A-bu-du-wei-li, Guo T, et al; Application effect and microbial ecological reconstruction analysis of probiotic regulation combined with photodynamic therapy in peri-implantitis. J North Sichuan Med Coll. 2025;40(8):991–6.
14. Hu MN, Sun F, Zhou YH. Clinical and microbiological effects of Lactobacillus reuteri as adjuvant therapy for peri-implantitis. Chin J Microecol. 2019;31(8):934–9.
15. Li SN, Song W. Effect of semiconductor laser on treatment of mild-to-moderate periimplantitis. Chin J Nosocomiol. 2023;33(13):2032–6.
16. Liu Y, Fan ZH, Yang CHSH. Short-term effect of implant grinding and polishing combined with drugs and laser therapy on peri-implantitis. J Mod Stomatol. 2023;37(6):401–6.
17. Liu XX, Ma X, Yang SY. Efficacy of photodynamic therapy as an adjunct in the treatment of peri-implantitis. Acta Univ Med Anhui. 2018;53(4):645–8.
18. Tian XM, Liu YQ, Li L, et al; Clinical study on joint application of Er,Cr:YSGG laser and implant polishing in treating peri-implantitis. Chin J Laser Med Surg. 2023;32(6):306–12.
19. Zhao YJ, Li RH, Ren G, et al; Effect of low-level laser treatment combined with initial periodontal therapy on IL-8, b-FGF, and IL-1β content in gingival crevicular fluid in peri-implantitis. Int J Biomed Eng. 2019;42(2):130–3.
20. Soysal F, Unsal B, Isler SC, Akca G, Bakirarar B, Ozcan M. Evaluation of salivary stress markers and inflammatory cytokine levels in patients with peri-implantitis. Clin Oral Invest. 2024;28(5):290.
21. Chmielewski M, Pilloni A. Current molecular, cellular, and genetic aspects of peri-implantitis disease: a narrative review. Dent J-Basel. 2023;11(5):134.
22. Guarnieri R, Reda R, Di Nardo D, et al; Expression of IL-1β, IL-6, TNF-α, and a-MMP-8 in sites with healthy conditions and with periodontal and peri-implant diseases: a case-control study. J Dent Res Dent Clin Dent Prospects. 2024;18(2):135–42.
23. Nart J, Pons R, Valles C, Esmatges A, Sanz-Martín I, Monje A. Non-surgical therapeutic outcomes of peri-implantitis: 12-month results. Clin Oral Invest. 2020;24(2):675–82.
24. Elsadek MF. Effectiveness of 2 photosensitizer-mediated photodynamic therapies for treating moderate peri-implant infections in patients with type 2 diabetes mellitus: a randomized clinical trial. Photodiagn Photodyn Ther. 2023;43:103643.
25. Almoharib H. Erbium-doped yttrium aluminum garnet (Er:YAG) lasers in the treatment of peri-implantitis. Cureus J Med Science. 2025;17(1):e78279.
26. Chen JH, Lin YC, Kung JC, et al; Efficacy of Er:YAG laser for peri-implantitis treatment and microbiological changes: a randomized controlled trial. Laser Med Sci. 2022;37(9):3517–25.
27. Świder K, Dominiak M, Grzech-Leśniak K, Matys J. Effect of different laser wavelengths on periodontopathogens in peri-implantitis: a review of in vivo studies. Microorganisms. 2019;7(7):189.
28. Neophytou C, Vlachodimou E, Kaklamanos EG, Sakellari D, Papadimitriou K. Microbiological effects of laser-assisted non-surgical treatment of peri-implantitis: a systematic review and meta-analysis of randomized controlled trials. Dent J-Basel. 2026;14(1):49.
29. Sun D, Li Z, Li D, Wu B, Ma Y. Laser combined with mechanical debridement enhances pain relief and inflammation control in the management of periodontitis with peri-implantitis. Am J Transl Res. 2025;17(7):5698–5709.
| Files | ||
| Issue | Articles in Press | |
| Section | Original Article(s) | |
| Keywords | ||
| Cytokines Gingival crevicular fluid Laser therapy peri-implantitis Photochemotherapy | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Zhu W, Hong F, Wang L. Immune-inflammatory Modulation by Non-surgical Therapies in Peri-implantitis. Iran J Allergy Asthma Immunol. 2026;:1-12.
