The Interaction of Cytokines in Orthodontics: A Systematic Review
Source abstract
Abstract
Aim: Cytokines are crucial low-molecular-weight proteins involved in immune responses. This systematic review highlights the need for in-depth studies on cytokines’ biological mechanisms, providing insights into disease onset and potential therapeutic strategies. Materials and methods: A comprehensive literature search identified 18 relevant articles, emphasizing the multifaceted role of cytokines in orthodontic treatment (OT). The quality assessment using the ROBINS-I tool ensures a rigorous evaluation of the included studies, contributing to the overall reliability of the findings. Results and Conclusions: This systematic review explores the intricate relationship between cytokines and OT. Cytokines exhibit different properties, influencing cellular activities through autocrine, paracrine, and endocrine activities. OT, aimed at achieving stable occlusion, induces tension and compression in the periodontal ligament (PDL), triggering cytokine release. Proinflammatory cytokines play a role in inflammation, influencing bone and soft tissue metabolism. Studies show elevated cytokine levels in gingival crevicular fluid (GCF) after orthodontic force application. The choice of orthodontic devices, such as self-ligating brackets, influences cytokine concentrations, indicating the importance of attachment design. Further research promises to enhance orthodontic practices, and optimize patient care.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Orthodontics and Dentofacial Orthopedics · Osteoarthritis Treatment and Mechanisms · Oral microbiology and periodontitis research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy
Implant Dentistry College of Medicine and Dentistry Birmingham, University of Birmingham, Birmingham B4 6BN, UK
References (100+)
Show source-provided references
1. (2024, January 28). Cytokine Storm and Sepsis Disease Pathogenesis, Available online: https://pubmed.ncbi.nlm.nih.gov/28555385/.
2. Pfaff, D.W., Volkow, N.D., and Rubenstein, J.L. (2022). Neuroimmune Signaling: Cytokines and the Central Nervous System. Neuroscience in the 21st Century, Springer International Publishing.
3. Cytokine Networking of Innate Immunity Cells: A Potential Target of Therapy10.1042/CS20130497 ↗
4. Pro- and Anti-Inflammatory Responses Are Regulated Simultaneously from the First Moments of Septic Shock10.1684/ecn.2011.0281 ↗
5. Training Innate Immunity: The Changing Concept of Immunological Memory in Innate Host Defence10.1111/eci.12132 ↗
6. Cytokine Therapy10.1016/j.hoc.2018.12.004 ↗
7. Dictionary of Immune Responses to Cytokines at Single-Cell Resolution10.1038/s41586-023-06816-9 ↗
8. Jarczak, D., and Nierhaus, A. (2022). Cytokine Storm-Definition, Causes, and Implications. Int. J. Mol. Sci., 23.10.3390/ijms231911740 ↗
9. (2024, January 28). Structural Biology of Shared Cytokine Receptors, Available online: https://pubmed.ncbi.nlm.nih.gov/18817510/.
10. Thomson, A.W., Lotze, M.T., Thomson, A.W., and Lotze, M.T. (2003). The Cytokine Handbook, Two-Volume Set, Academic Press. [4th ed.].
11. An Alternative “Trojan Horse” Hypothesis for COVID-19: Immune Deficiency of IL-10 and SARS-CoV-2 Biology10.2174/1871530321666210127141945 ↗
12. Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy10.1016/j.immuni.2013.01.004 ↗
13. Ergoren, M.C., Paolacci, S., Manara, E., Dautaj, A., Dhuli, K., Anpilogov, K., Camilleri, G., Suer, H.K., Sayan, M., and Tuncel, G. (2020). A Pilot Study on the Preventative Potential of Alpha-Cyclodextrin and Hydroxytyrosol against SARS-CoV-2 Transmission. Acta Bio Medica Atenei Parm., 91.
14. Inchingolo, A.D., Dipalma, G., Inchingolo, A.M., Malcangi, G., Santacroce, L., D’Oria, M.T., Isacco, C.G., Bordea, I.R., Candrea, S., and Scarano, A. (2021). The 15-Months Clinical Experience of SARS-CoV-2: A Literature Review of Therapies and Adjuvants. Antioxidants, 10.10.3390/antiox10060881 ↗
15. Periodontal Disease and Bone Pathogenesis: The Crosstalk between Cytokines and Porphyromonas Gingivalis
16. Effect of Probiotics on the Occurrence of Nutrition Absorption Capacities in Healthy Children: A Randomized Double-Blinded Placebo-Controlled Pilot Study
17. Inchingolo, A.D., Carpentiere, V., Piras, F., Netti, A., Ferrara, I., Campanelli, M., Latini, G., Viapiano, F., Costa, S., and Malcangi, G. (2022). Orthodontic Surgical Treatment of Impacted Mandibular Canines: Systematic Review and Case Report. Appl. Sci., 12.10.3390/app12168008 ↗
18. Induction of Cytokines, MMP9, TIMPs, RANKL and OPG during Orthodontic Tooth Movement10.1093/ejo/cjs057 ↗
19. Cytokine Measurements in Gingival Crevicular Fluid and Periodontal Ligament: Are They Correlated?10.1016/j.ajodo.2015.03.030 ↗
20. Oral Microbiome and Preterm Birth10.3389/fmed.2023.1177990 ↗
21. Inchingolo, F., Inchingolo, A.D., Palumbo, I., Trilli, I., Guglielmo, M., Mancini, A., Palermo, A., Inchingolo, A.M., and Dipalma, G. (2024). The Impact of Cesarean Section Delivery on Intestinal Microbiota: Mechanisms, Consequences, and Perspectives-A Systematic Review. Int. J. Mol. Sci., 25.10.3390/ijms25021055 ↗
22. Inchingolo, F., Martelli, F.S., Gargiulo Isacco, C., Borsani, E., Cantore, S., Corcioli, F., Boddi, A., Nguyễn, K.C.D., De Vito, D., and Aityan, S.K. (2020). Chronic Periodontitis and Immunity, Towards the Implementation of a Personalized Medicine: A Translational Research on Gene Single Nucleotide Polymorphisms (SNPs) Linked to Chronic Oral Dysbiosis in 96 Caucasian Patients. Biomedicines, 8.10.3390/biomedicines8050115 ↗
23. Di Francesco, F., Lanza, A., Di Blasio, M., Vaienti, B., Cafferata, E.A., Cervino, G., Cicciù, M., and Minervini, G. (2022). Application of Botulinum Toxin in Temporomandibular Disorders: A Systematic Review of Randomized Controlled Trials (RCTs). Appl. Sci., 12.10.3390/app122312409 ↗
24. Crescente, G., Minervini, G., Spagnuolo, C., and Moccia, S. (2022). Cannabis Bioactive Compound-Based Formulations: New Perspectives for the Management of Orofacial Pain. Molecules, 28.10.3390/molecules28010106 ↗
25. Biologically-Oriented Alveolar Ridge Preservation10.23736/S2724-6329.23.04776-9 ↗
26. Biomechanical Characteristics of Orthodontic Tooth Movement before and after Increasing Alveolar Bone Mass with Periodontally Accelerated Osteogenic Orthodontics
27. Comparison of Postoperative Serum Biomarkers after Total Hip Arthroplasty through Minimally Invasive versus Conventional Approaches: A Systematic Review and Meta-Analysis of Randomized Controlled Trials10.3390/prosthesis5030049 ↗
28. (2024, January 28). Osteoclast Activating Factor Is Now Interleukin-1 Beta: Historical Perspective and Biological Implications, Available online: https://pubmed.ncbi.nlm.nih.gov/3139850/.
29. (2024, January 28). Effects of Aging on RANKL and OPG Levels in Gingival Crevicular Fluid during Orthodontic Tooth Movement, Available online: https://pubmed.ncbi.nlm.nih.gov/16918678/.
30. Osteoclast Differentiation and Activation10.1038/nature01658 ↗
31. Matrix Metalloproteinases and Th17 Cytokines in the Gingival Crevicular Fluid during Orthodontic Tooth Movement
32. Levels of Matrix Metalloproteinases 1 and 2 in Human Gingival Crevicular Fluid during Initial Tooth Movement10.1016/j.ajodo.2006.04.020 ↗
33. (2024, January 28). Expression of Genes for Gelatinases and Tissue Inhibitors of Metalloproteinases in Periodontal Tissues during Orthodontic Tooth Movement, Available online: https://pubmed.ncbi.nlm.nih.gov/17043917/.
34. Interleukin (IL)-1 Beta, IL-6, Tumor Necrosis Factor-Alpha, Epidermal Growth Factor, and Beta 2-Microglobulin Levels Are Elevated in Gingival Crevicular Fluid during Human Orthodontic Tooth Movement10.1177/00220345960750010801 ↗
35. A Perspective on Prosthetic Hands Control: From the Brain to the Hand10.3390/prosthesis5040083 ↗
36. Early Treatment of Class II Division 1 Malocclusions with Prefabricated Myofunctional Appliances: A Case Report10.3390/prosthesis5040073 ↗
37. Extraction of Mandibular Third Molars: Proposal of a New Scale of Difficulty10.1016/j.bjoms.2017.09.012 ↗
38. Five-Year Follow-Up of 8 and 6 Mm Locking-Taper Implants Treated with a Reconstructive Surgical Protocol for Peri-Implantitis: A Retrospective Evaluation10.3390/prosthesis5040091 ↗
39. Pharyngeal Obturator Prosthesis Ideal for Orthodontic Appliances: A Case Series10.3390/prosthesis5040079 ↗
40. Single Crown Restorations Supported by One-Piece Zirconia Dental Implants: Case Series with a Mean Follow-Up of 58 Months10.3390/prosthesis5040074 ↗
41. The Role of Cognitive and Non-cognitive Factors in Dental Anxiety: A Mediation Model10.1111/eos.12793 ↗
42. Tooth Movement, Orofacial Pain, and Leptin, Interleukin-1β, and Tumor Necrosis Factor-α Levels in Obese Adolescents10.2319/011321-44.1 ↗
43. Cytokine Gene Polymorphisms Associate with Microbiogical Agents in Periodontal Disease: Our Experience10.7150/ijms.6962 ↗
44. Balzanelli, M.G., Distratis, P., Lazzaro, R., Pham, V.H., Tran, T.C., Dipalma, G., Bianco, A., Serlenga, E.M., Aityan, S.K., and Pierangeli, V. (2022). Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection. Diagnostics, 12.10.3390/diagnostics12112824 ↗
45. Montemurro, N., Perrini, P., Marani, W., Chaurasia, B., Corsalini, M., Scarano, A., and Rapone, B. (2021). Multiple Brain Abscesses of Odontogenic Origin. May Oral Microbiota Affect Their Development? A Review of the Current Literature. Appl. Sci., 11.10.3390/app11083316 ↗
46. Inchingolo, A.D., Inchingolo, A.M., Bordea, I.R., Malcangi, G., Xhajanka, E., Scarano, A., Lorusso, F., Farronato, M., Tartaglia, G.M., and Isacco, C.G. (2021). SARS-CoV-2 Disease through Viral Genomic and Receptor Implications: An Overview of Diagnostic and Immunology Breakthroughs. Microorganisms, 9.10.3390/microorganisms9040793 ↗
47. Inchingolo, A.D., Gargiulo, C.I., Malcangi, G., Ciocia, A.M., Patano, A., Azzollini, D., Piras, F., Barile, G., Settanni, V., and Mancini, A. (2022). Diagnosis of SARS-CoV-2 during the Pandemic by Multiplex RT-rPCR hCoV Test: Future Perspectives. Pathogens, 11.10.3390/pathogens11111378 ↗
48. (2024, February 01). SARS-CoV-2 Disease Adjuvant Therapies and Supplements Breakthrough for the Infection Prevention, Available online: https://pubmed.ncbi.nlm.nih.gov/33806624/.
49. The Safety of Blinatumomab in Pediatric Patients with Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis10.3389/fped.2022.929122 ↗
50. Di Paola, A., Tortora, C., Argenziano, M., Marrapodi, M.M., and Rossi, F. (2022). Emerging Roles of the Iron Chelators in Inflammation. Int. J. Mol. Sci., 23.10.3390/ijms23147977 ↗
51. Cytokine Genotype Distribution in Patients with Periodontal Disease and Rheumatoid Arthritis or Diabetes Mellitus
52. The Effect of Obesity on Orofacial Pain during Early Orthodontic Treatment with Fixed Appliances: A Prospective Cohort Study10.1093/ejo/cjx064 ↗
53. Obesidade e adipocinas inflamatórias: Implicações práticas para a prescrição de exercício10.1590/S1517-86922009000600012 ↗
54. Malcangi, G., Patano, A., Ciocia, A.M., Netti, A., Viapiano, F., Palumbo, I., Trilli, I., Guglielmo, M., Inchingolo, A.D., and Dipalma, G. (2023). Benefits of Natural Antioxidants on Oral Health. Antioxidants, 12.10.3390/antiox12061309 ↗
55. Inchingolo, F., Inchingolo, A.M., Latini, G., Ferrante, L., Trilli, I., Del Vecchio, G., Palmieri, G., Malcangi, G., Inchingolo, A.D., and Dipalma, G. (2023). Oxidative Stress and Natural Products in Orthodontic Treatment: A Systematic Review. Nutrients, 16.10.3390/nu16010113 ↗
56. (2024, January 27). Profiles of Inflammation Factors and Inflammatory Pathways around the Peri-Miniscrew Implant, Available online: https://pubmed.ncbi.nlm.nih.gov/33834451/.
57. (2024, January 28). Interleukin-17, RANKL, and Osteoprotegerin Levels in Gingival Crevicular Fluid from Smoking and Non-Smoking Patients with Chronic Periodontitis during Initial Periodontal Treatment, Available online: https://pubmed.ncbi.nlm.nih.gov/19656027/.
58. (2024, January 28). LOX-1 Is Involved in IL-1β Production and Extracellular Matrix Breakdown in Dental Peri-Implantitis, Available online: https://pubmed.ncbi.nlm.nih.gov/28898769/.
59. Osteopontin Is Essential for IL-1β Production and Apoptosis in Peri-Implantitis10.1111/cid.12592 ↗
60. Quantification of Pro-Inflammatory Cytokines and Osteoclastogenesis Markers in Successful and Failed Orthodontic Mini-Implants10.1590/1678-7757-2018-0476 ↗
61. A Review of Biomarkers in Peri-Miniscrew Implant Crevicular Fluid (PMICF)10.1186/s40510-017-0195-8 ↗
62. (2024, January 27). Cytokine Profile Changes in Gingival Crevicular Fluid after Placement Different Brackets Types, Available online: https://pubmed.ncbi.nlm.nih.gov/29032048/.
63. OPG and RANKL Levels around Miniscrew Implants during Orthodontic Tooth Movement10.1016/j.ajodo.2013.02.028 ↗
64. Brambilla, E., Locarno, S., Gallo, S., Orsini, F., Pini, C., Farronato, M., Thomaz, D.V., Lenardi, C., Piazzoni, M., and Tartaglia, G. (2022). Poloxamer-Based Hydrogel as Drug Delivery System: How Polymeric Excipients Influence the Chemical-Physical Properties. Polymers, 14.10.3390/polym14173624 ↗
65. (2024, January 28). Gingival Crevicular Fluid Volume and Periodontal Parameters Alterations after Use of Conventional and Self-Ligating Brackets, Available online: https://pubmed.ncbi.nlm.nih.gov/27607519/.
66. (2024, January 28). Alterations in Plaque Accumulation and Gingival Inflammation Promoted by Treatment with Self-Ligating and Conventional Orthodontic Brackets, Available online: https://pubmed.ncbi.nlm.nih.gov/25992985/.
67. (2024, January 27). Gingival Crevicular Fluid Bone Turnover Biomarkers: How Postmenopausal Women Respond to Orthodontic Activation, Available online: https://pubmed.ncbi.nlm.nih.gov/28651765/.
68. (2024, January 28). Receptor Activator of NF(Kappa)B Ligand/Osteoprotegerin (RANKL/OPG) System and Osteopontin (OPN) Serum Levels in a Population of Apulian Postmenopausal Women, Available online: https://pubmed.ncbi.nlm.nih.gov/17215793/.
69. Comparison of Expression Levels of RANKL and Interleukin-17A in Male and Female Orthodontic Patients with and without Appliances10.11607/prd.1886 ↗
70. Gender Medicine: The Impact of Probiotics on Male Patients
71. Baeshen, H.A. (2021). Assessment of Salivary pro Inflammatory Cytokines Profile Level in Patients Treated with Labial and Lingual Fixed Orthodontic Appliances. PLoS ONE, 16.10.1371/journal.pone.0249999 ↗
72. Comparative Analysis of Growth Factors and Chemokine Secretions between Conventional Lingual and Labial Fixed Orthodontic Appliances10.4103/njcp.njcp_493_20 ↗
73. Effectiveness of Lingual versus Labial Fixed Appliances in Adults According to the Peer Assessment Rating Index10.1016/j.ajodo.2018.07.018 ↗
74. Cytokine Levels in Gingival Crevicular Fluid Samples of Patients Wearing Clear Aligners10.1016/j.jobcr.2020.04.005 ↗
75. Comparative Study of 660 and 830 Nm Photobiomodulation in Promoting Orthodontic Tooth Movement
76. (2024, January 28). Photobiomodulation Impacts the Levels of Inflammatory Mediators during Orthodontic Tooth Movement? A Systematic Review with Meta-Analysis, Available online: https://pubmed.ncbi.nlm.nih.gov/34599400/.
77. Effective Wavelength Range in Photobiomodulation for Tooth Movement Acceleration in Orthodontics: A Systematic Review
78. Fernandes, M.R.U., Suzuki, S.S., Suzuki, H., Martinez, E.F., and Garcez, A.S. (2019). Photobiomodulation Increases Intrusion Tooth Movement and Modulates IL-6, IL-8 and IL-1β Expression during Orthodontically Bone Remodeling. J. Biophotonics, 12.10.1002/jbio.201800311 ↗
79. Systematic Review of Orthodontic Treatment Management with Photobiomodulation Therapy10.1089/photob.2019.4702 ↗
80. (2024, January 28). Current Protocol to Achieve Dental Movement Acceleration and Pain Control with Photo-Biomodulation, Available online: https://pubmed.ncbi.nlm.nih.gov/38229945/.
81. Inchingolo, A.M., Malcangi, G., Inchingolo, A.D., Mancini, A., Palmieri, G., Di Pede, C., Piras, F., Inchingolo, F., Dipalma, G., and Patano, A. (2023). Potential of Graphene-Functionalized Titanium Surfaces for Dental Implantology: Systematic Review. Coatings, 13.10.3390/coatings13040725 ↗
82. Cytokines, Inflammation and Pain10.1097/AIA.0b013e318034194e ↗
83. Cascade of Immune Mechanism and Consequences of Inflammatory Disorders10.1016/j.phymed.2021.153712 ↗
84. Cytokines in the Treatment of Cancer10.1089/jir.2018.0019 ↗
85. Effect of Orthodontic Force on Expression Levels of Ten Cyto kines in Gingival Crevicular Fluid10.1016/j.archoralbio.2017.01.016 ↗
86. Evaluation of Interleukin-1β Level and Oxidative Status in Gingival Crevicular Fluid during Rapid Maxillary Expansion10.1016/j.archoralbio.2018.02.020 ↗
87. Evaluation of Periodontal Parameters and Gingival Crevicular Fluid Cytokines in Children with Anterior Open Bite Receiving Passive Orthodontic Treatment with a Spur10.4041/kjod.2022.52.2.142 ↗
88. (2024, January 26). Correlation of Salivary Cytokine Il-17a and 1,25 Dihydroxycholecalciferol in Patients Undergoing Orthodontic Treatment. Available online: https://www.researchgate.net/publication/371320269_Correlation_of_Salivary_Cytokine_Il-17a_and_125_Dihydroxycholecalciferol_in_Patients_Undergoing_Orthodontic_Treatment.
89. A Comparative Study on the IL-8 Expression in Gingival Crevicular Fluid during Early Alignment Stage of Orthodontic Treatment in Adults and Adolescents
90. RANKL Concentrations in Early Orthodontic Treatment Using Passive Self-Ligating and Preadjusted Edgewise Appliance Bracket Systems10.1088/1742-6596/1073/4/042002 ↗
91. Cytokine Levels in Gingival Crevicular Fluid during Orthodontic Treatment with Aligners Compared to Conventional Labial Fixed Appliances: A 3-Week Clinical Study10.1080/00016357.2019.1607548 ↗
92. (2024, January 26). Comparison of Tumor Necrosis Factor-α Concentrations in Gingival Crevicular Fluid between Self-Ligating and Preadjusted Edgewise Appliances in the Early Leveling Stage of Orthodontic Treatment, Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863418/.
93. Liu, Q., Guo, T., Dang, W., Song, Z., Wen, Y., Luo, H., and Wang, A. (2023). Correlation between Salivary Cytokine Profiles and White Spot Lesions in Adolescent Patients Receiving Clear Aligner Orthodontic Treatment. BMC Oral Health, 23.10.1186/s12903-023-03561-3 ↗
94. Glucosamine Oral Administration as an Adjunct to Hyaluronic Acid Injection in Treating Temporomandibular Joint Osteoarthritis10.1111/odi.12760 ↗
95. Comparison of Crevicular Fluid Cytokine Levels after the Application of Surface Sealants: A Randomized Trial10.1007/s00056-019-00184-8 ↗
96. Cytokine Expression and Accelerated Tooth Movement10.1177/0022034510373764 ↗
97. Assessment and Measurement of Interleukin 6 in Periodontal Ligament Tissues during Orthodontic Tooth Movement10.5005/jp-journals-10015-1610 ↗
98. Chelărescu, S., Șurlin, P., Decusară, M., Oprică, M., Bud, E., Teodorescu, E., Elsaafin, M.N., and Păcurar, M. (2021). Evaluation of IL1β and IL6 Gingival Crevicular Fluid Levels during the Early Phase of Orthodontic Tooth Movement in Adolescents and Young Adults. Appl. Sci., 11.10.3390/app11020521 ↗
99. Şahin, E., Cetinkaya, B.O., Avci, B., Kurt-Bayrakdar, S., and Elekdag-Turk, S. (preprint, 2022). Human Randomized Controlled Trail Clinical and Biochemical Evaluation Oral Irrigator Effectiveness in Patients Under Orthodontic Treatment, preprint.10.21203/rs.3.rs-2256671/v1 ↗
100. Influence of Anxiety and Catastrophizing on Pain Perception in Orthodontic Treatment and Its Association with Inflammatory Cytokines10.1590/1807-3107bor-2023.vol37.0010 ↗