|Year : 2018 | Volume
| Issue : 9 | Page : 1150-1157
Clinical and biochemical effects of erbium, chromium: yttrium, scandium, gallium, garnet laser treatment as a complement to periodontal treatment
K Ustun1, M Hatipoglu1, O Daltaban1, R Felek2, MZ Firat3
1 Department of Periodontology, Faculty of Dentistry, Akdeniz University, Antalya, Turkey
2 Department of Basic Science, Faculty of Dentistry, Akdeniz University, Antalya, Turkey
3 Department of Genetics and Biometrics, Faculty of Agriculture, Akdeniz University, Antalya, Turkey
|Date of Acceptance||21-Mar-2018|
|Date of Web Publication||29-Aug-2018|
Prof. M Hatipoglu
Department of Periodontology, Akdeniz University, Faculty of Dentistry, 07058 Antalya
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: The purpose of this study was to investigate the clinical effects of erbium, chromium: yttrium, scandium, gallium, garnet (Er, Cr: YSGG) laser treatment as a complementary to scaling and root planning (SRP) during the treatment of chronic periodontitis and gingival crevicular fluid (GCF) interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-35 (IL-35) levels. Materials and Methods: Forty patients with chronic periodontitis were divided into two equal groups at random to receive SRP alone and SRP followed by Er, Cr: YSGG laser treatment, which are control and test groups, respectively. Clinical attachment level (CAL), probing depth (PD), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) were measured for all patients in both groups at baseline and again at the end of the 1st, 3rd, and 6th months following the treatment. Levels of GCF IL-1β, IL-6, and IL-35 were analyzed by enzyme-linked immunosorbent assay. Results: After periodontal treatment, CAL, PD, BOP, GI, and PI, which are clinical parameters analyzed, decreased significantly (P < 0.05) in both test and control groups. GCF volume, IL-1 β, IL-6, and IL-35, levels in both groups proved statistically significant reductions compared to the baseline (P < 0.05), but no substantial variations were detected among both groups. Conclusion: According to these results, we can suggest that IL-35 may be related to the pathogenesis of periodontitis and that Er, Cr: YSGG laser can be used as an adjunct to SRP in periodontal treatment.
Keywords: Erbium, chromium: yttrium, scandium, gallium, garnet laser, interleukin-35, periodontitis
|How to cite this article:|
Ustun K, Hatipoglu M, Daltaban O, Felek R, Firat M Z. Clinical and biochemical effects of erbium, chromium: yttrium, scandium, gallium, garnet laser treatment as a complement to periodontal treatment. Niger J Clin Pract 2018;21:1150-7
|How to cite this URL:|
Ustun K, Hatipoglu M, Daltaban O, Felek R, Firat M Z. Clinical and biochemical effects of erbium, chromium: yttrium, scandium, gallium, garnet laser treatment as a complement to periodontal treatment. Niger J Clin Pract [serial online] 2018 [cited 2021 Jan 21];21:1150-7. Available from: https://www.njcponline.com/text.asp?2018/21/9/1150/240070
| Introduction|| |
Periodontal disease is characterized by chronic inflammation of the supporting periodontal tissues, which is mediated by the host immune and inflammatory response to the microbial dental plaqueflora. Elimination of supra- and subgingival bacterial deposits is the basic and long-term aspect of periodontal treatment for preventing the progression of disease and maintaining the periodontal health. Scaling and root planning (SRP) is commonly used as a nonsurgical periodontal treatment method and its clinical efficacy has been demonstrated in several clinical studies., Mechanical periodontal treatment alone, on the other hand, is not all the time prognosticated and has some limitations for completely eradicating pathogenic bacteria and toxins within deep periodontal pockets and in complex root morphologies that are inaccessible by periodontal instruments., Furthermore, mechanical instrumentations have been shown to produce a smear layer that contains microbiota and its products that may affect the periodontal healing and can lead to residual periodontal pocketing and bacterial recolonization.,
To overcome these limitations and improve the effectiveness of the treatment, new technical modalities, such as laser systems, have also been used as a complementary or alternative therapy to mechanical periodontal treatment due to several advantages.,, The erbium, chromium: yttrium, scandium, gallium, garnet (Er, Cr: YSGG) laser (2.78 mm), which has an active medium of YSGG doped with chromium and erbium and emits free-running pulsed laser energy at 2780 nm, has been successfully used in periodontal treatment., Several studies have shown that this laser, in a suitable wavelength, promotes calculus removal without thermal damages and may effectively remove smear layer and have strong bactericidal effects to reduce the amount of the bacterial population in the periodontal pocket.,,
However, the anti-inflammatory and antimicrobial effects of laser treatment on the periodontal tissue are still not completely understood. Microbial agents that host immune responses and environmental factors collectively provoke host responses and result in releasing biologic mediators such as cytokines. Increase in cytokine production results in periodontal tissue damage, and various cytokines have been detected in gingival crevicular fluid (GCF).
IL-6, which is generated by host cells, is a valuable cytokine in the regulation of host response and it has a key function in B-cell differentiation, T-cell proliferation and also IL-6 is synergistic with interleukin-1 beta (IL-1 β) that induces bone resorption., The proinflammatory cytokine IL-1 β also adjusts prostaglandins production, as well as encouraging the formation of osteoclasts and bone resorption. IL-1 β has been demonstrated to be considerably reproduced in the periodontal tissues and also gingival fluid from diseased areas considering the healthy areas. Monitoring IL-1 β levels was suggested in order to compare treatment outcomes by many authors.,,
IL-35, the newest member of IL-12 cytokine family, is a potent inhibitory cytokine produced by natural, thymus-derived regulatory T-cell (nTreg) populations. It has been reported that IL-35 inhibits T-cell proliferation, induces the development of an induced regulatory T-cell (iTreg) population, and also suppresses T-cell proliferation by inducing cell cycle arrest in G1 without inducing apoptosis.,, More recently, it has been shown that IL-35 appears to take part like an immunomodulatory agent in many disease cases., The expression of IL-35 mRNA in gingival tissues and GCF levels in chronic periodontitis versus healthy has been demonstrated and it has been suggested that IL-35 is associated with the pathogenesis of periodontitis., In our literature review, however, there was no study comparing the effects of periodontal treatment on GCF IL-35 levels. Being able to potentially influence the advancement of periodontal disease, proinflammatory cytokines can also determine clinical treatment's effectiveness. The aim of this study was to investigate the effects of laser treatment (Er, Cr:YSGG) in chronic periodontitis patients using clinical parameters and GCF IL-1β, IL-6, and IL-35 levels.
| Materials and Methods|| |
The study carried out was a controlled and randomized clinical trial using a parallel design. Forty patients, who have chronic periodontitis and were referred to the Department of Periodontology, Faculty of Dentistry, Akdeniz University, for periodontal treatment, were appointed in two groups of equal number by a random selection to get SRP and laser (test group) or SRP alone (control group). Coin toss method was used for randomization. [Table 1] represents the demographic characteristics of the study groups.
While written consent of all individuals was taken before the study, the protocol submitted to Akdeniz University Ethics Committee (2014-180) for the participation of human subjects has been accepted.
Patients having at least 2 teeth with ≥5 mm probing pocket depth (PPD) were included in every quadrant provided that they had at least 14 teeth in their mouths. The exclusion criterion was a history of any systemic diseases that may influence the periodontal therapy outcome, for example, diabetes mellitus, cancer, metabolic or endocrine diseases, smoking, dental treatment in the past 6 months, antibiotic medication during the 6 months preceding the study, and related teeth with restoration.
Treatment protocols and laser parameters
All patients received periodontal therapy at first which consisted of comprehensive instructions on oral hygiene and supragingival scaling for the whole mouth with the combined use of hand (Hu-Friedy, Chicago, IL, USA) and ultrasonic instruments (EMS, Nyon, Switzerland). Each treatment was carried out 1 week apart. SRP was performed in a single appointment under local anesthesia. For laser groups, laser was applied in the same appointment. Er, Cr: YSGG laser (Waterlase® iplus, Biolase, Irvine CA, USA) treatment was performed with a RFPT 5–14 tip at 1.5 W 30 Hz, 15% Air, 15% H2O H mode (pulse duration 140 ms). During the application of laser treatment, protective goggles were used both by the patient and by the operator.
Clinical periodontal parameters were evaluated at the baseline and after 1, 3, and 6 months following the treatment. The patients' periodontal statuses were assessed using thorough standard periodontal parameters. The assessed parameters were clinical attachment level (CAL), probing depth (PD), plaque index (PI), and gingival index (GI). While PD is specified as the measurement between the bottom of the periodontal pocket and the free gingival margin, CAL is defined as the measurement from bottom of the periodontal pocket to cementoenamel junction. These distance measurements of PD and CAL were recorded by a manual periodontal probe at six points (mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual, and distolingual) around each tooth (PWD, Hu-Friedy, Chicago, IL, USA).
Gingival crevicular fluid sampling
At the baseline and after 1, 3, and 6 months, GCF samples were compiled from the same tooth of every quadrant. The collections were performed as previously described by Köseoğlu et al., and as soon as the samples were collected, they were immediately stored at −20°C before analysis.
During the analysis of GCF samples for IL-1 β (Invitrogen™ Corporation 542 Flynn Road, Camarillo, CA, USA), IL-35 (Uscn Life Science Inc., Wuhan, China), and IL-6 (DIAsource ImmunoAssays S. A.-Rue de l'Industrie, 8-B-1400, Nivelles, Belgium), a commercial kit was used in line with the instructions of the manufacturer. The plate was analyzed at a wavelength of 450 nm using an enzyme-linked immunosorbent assay reader (SEAC RADIM Company, Sirios model EAC, via di Prato, 72–74, Firenze, Italy).
SAS version 9.3 (SAS Institute, Cary, NC, USA), which is a commercially available software, was used for the statistical analysis. Descriptive statistics, such as the average and standard deviation (SD), were used to describe the main variables. The Shapiro–Wilks normality test was conducted to assess the variables' normality to use a parametric or nonparametric test. Parametric tests had been used within the groups (repeated measures analysis of variance/Tukey's test) and between the groups (two-tailed paired Student's t-test) during testing (whole-mouth clinical variables/site-specific clinical variables and all biochemical variables) since all variables were normally distributed. Associations between the whole-mouth clinical variables/site-specific clinical variables and all biochemical variables were investigated using Pearson's correlation test. A two-sided P < 0.05 was considered statistically significant for all analysis.
| Results|| |
All the data were entered, checked for missing values, and analyzed using the statistical methods described in the previous section. [Table 1] illustrates the baseline demographic data of 40 patients participated in the study, where 19 patients were female and 21 patients were male. Average ages of patients in control and test groups were 44.05 and 45.80, respectively.
The statistical results of the clinical measurements, such as probing depth (PD), CAL, PI, GI, and bleeding on probing (BOP) as average ± SD, in test and control groups between baseline and 1st, 3rd, and 6th months are both presented in [Table 2] and [Figure 1], respectively. As shown in [Table 1], all whole-mouth clinical variables represented statistically significant reductions at all given times compared to baseline in both test group and control group (P < 0.05). Comparing the average values at the 1st month, significant reductions were observed in the average values of GI and BOP at the 6th month for both groups. The changes in BOP after the 1st and 3rd months were also substantially higher for both groups (P < 0.05). On the other hand, the change in GI after the 1st and 3rd months was only significantly higher for the control groups (P < 0.05). At the 3rd month, the average values of BOP were also substantially higher than the average values recorded at the 6th month for both groups.
|Figure 1: Whole-mouth probing depth, clinical attachment level, plaque index, gingival index, bleeding on probing (percent) values and gingival crevicular fluid volume and interleukin-1 beta, interleukin-6, and interleukin-35 values|
Click here to view
In a comparison between control and test groups, only PD decreased for the test group (P < 0.05). In test group, the decrease of PD at the 1st month was statistically substantial compared to the control group.
The results of the biochemical and sampled-site clinical measurements (IL-1 β, IL-6, IL-35, GCF volume [GCFvol], PD, CAL, PI, and GI as average ± SD) are illustrated for the test and control groups in [Table 3]. Average values of IL-1 β, IL-6, GCFvol, PD, CAL, PI, and GI at baseline were substantially lower for both groups than the average values at the 1st, 3rd, and 6th months. No statistically significant differences were observed in IL-35 values between the time points in both groups. The change in IL-1 β, IL-6, GCFvol, PDs, and CALs after the 1st and 6th months and change in CALs at the same time points were considerably higher in test and control groups (P < 0.05). Furthermore, the change in PDs for the test group and change in GIs for the control group at months 1 and 3 were statistically substantial (P < 0.05). In a comparison between the 1st and 6th months, considerable differences were detected in GCFvol, CALs, and GIs values for the test group and also the average values of PDs and GIs after 3rd and 6th months were considerably lower in the control group.
Considering IL-1 β, IL-6, IL-35, GCFvol, PD, CAL, and PI parameters, there were no significant differences between test and control groups at any given time during the study [Table 3]. However, the decrease in GI was dramatically superior at the test group (P < 0.05). Substantial differences were observed between both groups at the 1st and 3rd months.
| Discussion|| |
Clinically, SRP with hand instruments have been proven as an effective treatment method for periodontal disease., The results of the study performed illustrated that periodontal treatment with either SRP alone or SRP followed by Er, Cr: YSGG laser treatment leads to both statistically and clinically important advancements in all analyzed clinical parameters (PI, GI, PD, BOP, and CAL) at the 1st, 3rd, and 6th months following treatment compared to baseline. Postoperative recovery was event free in all of the cases, which shows that nonsurgical periodontal treatment with SRP alone or in combination with Er, Cr: YSGG laser is well tolerated.
However, recent studies have demonstrated that complete removal of calculus and elimination of the microorganisms in the soft tissue wall of the pocket by manual instruments was often incomplete, and such treatment generally resulted in a smear layer, which holds bacteria and their products that may stimulate the process of periodontal tissue healing, on the surfaces of the root.,,
To overcome these disadvantages, laser system gains popularity in general dental practice and is suggested as a complementary or alternative method for periodontal treatment.,, Erbium family of lasers have been reported to be the most promising lasers for nonsurgical periodontal treatment.,, The effects of different power outputs of Er, Cr: YSGG laser on the root surfaces and the efficiency of calculus removal were examined by Ting et al., and the authors reported that a 1 W power output setting is suitable for root scaling and removing calculus without making any morphologic alterations on the root surface. Hakki et al. compared the mechanical treatment to Er, Cr: YSGG laser treatment for removing calculus and reported that laser therapy was effective on root surface ablation and could be practiced to achieve SRP during the course of periodontal disease treatment.
Practicing the Er, Cr: YSGG laser with root planning and scaling brought on statistically dramatic reductions of the full-mouth and site-specific probing depths (PD, PDs) compared to the outcomes achieved in SRP alone in 6 months after the treatment in the study performed. Furthermore, the site-specific CAL (CALs) improvement in the laser-treated group was statistically significant at 6 months after the treatment. This finding is in consistence with the results obtained from the previous studies.,, In a 2-year follow-up study, Crespi et al. found significant difference in the PD to favor Er: YAG treatment over conventional treatment with ultrasonic devices. Dyer and Sung demonstrated that Er, Cr: YSGG surgical laser treatment along with a standard conventional treatment in every 3 months in moderate-to-advanced periodontal disease brought on a serious reduction in pocket depths and also improved levels of clinical attachment 2 years posttreatment. In a 1-year clinical study, Kelbauskiene et al. compared SRP with Er, Cr: YSGG laser treatment in adjunct to SRP in patients with early-to-moderate periodontitis and showed that the average PD decrease and CAL increase were dramatically higher in SRP + laser-treated sites than in only SRP-treated sites and the most significant alterations of the PD were achieved in 6 months after the therapy.
In an in vitro study, Hakki et al. concluded that the micromorphology of the root surfaces prepared by laser may be more satisfactory for the repair of the periodontal attachment by showing that the surfaces prepared by laser were more biocompatible for periodontal fibroblast attachment compared to curette-treated root surfaces. Our results are in agreement with this notion and may suggest that since several studies demonstrated that Er, Cr: YSGG laser has bactericidal effects and can effectively remove calculus and smear layer from the root surface and allows for particular removal of sulcular or pocket epithelium, laser-treated root surface may enable more suitable environment for increased connective tissue attachment and may also enhance periodontal healing., This positive finding can indicate that Er, Cr: YSGG laser can be used as an adjunct to SRP in periodontal treatment.
Recent studies have shown that the laser radiation affects the production of cytokines and may modulate the oral inflammatory response. In this study, the GCFvol, IL-1 β, and IL-6 levels in both SRP and SRP + laser groups showed statistically important decreases at the times measured compared to the baseline, without showing substantial differences among the groups. There was a positive correlation between the levels of IL-1 β, IL-6, GCFvol, and clinical parameters (PI, GI, and BOP). GCF has been presented as a potential diagnostic value to assess the disease activity and periodontal treatment efficacy. The findings of this study in consistent with the previous studies indicated that the GCF levels of proinflammatory cytokines are higher in sites of inflammation, and reductions were seen after periodontal treatment.,,, Offenbacher et al. explained that patients with deep pocket depths and more severe BOP had increased GCF IL-1β and IL-6 levels. Miyazaki et al. analyzed the immunological effects and made a comparison between Nd: YAG laser monotherapy and ultrasonic scaling for nonsurgical treatment of patients with chronic periodontitis and reported that the intergroup analysis did not prove any statistical importance, even though the Nd: YAG group tended to achieve a reduction in IL-1 β, comparatively. Saglam et al. conducted a randomized, parallel, and controlled clinical trial to investigate the biochemical and clinical efficacy of diode laser as a complementary treatment to SRP in patients with chronic periodontitis and reported that the amounts of IL-1 β and IL-6 decreased (P < 0.05) following the treatments in both test group and control group (P < 0.05) with no statistically significant differences between groups. Eltas and Orbak compared the effects of Nd: YAG laser + SRP and SRP alone in chronic periodontitis patients by determining the clinical indices and levels of IL-1 β and matrix metalloproteinase-8 (MMP-8) in GCF before and after the treatment and found out that even though IL-1 β and MMP-8 levels in GCF following the treatment were reduced in the SRP + Nd:YAG laser (NDL) compared to the SRP, the differences were not statistically considerable (P > 0.05). On the other hand, Qadri et al. reported that levels of IL-1 β and MMP-8 substantially decreased by Nd: YAG laser treatment, indicating that laser type could play a key role on the results of the treatment. Gómez et al. presented a randomized clinical study to determine the clinical, microbiological, and anti-inflammatory efficacy of Nd: YAG laser in periodontal treatment as a complementary to SRP and found out that statistically significant differences for clinical or microbiological variables could not be observed between the treatments of SRP and SRP + Nd: YAG. On the other hand, the IL-1 β levels in GCF were substantially decreased following the SRP + Nd: YAG treatment.
T-cells have a significant key role in the regulatory immune response, and Gershon and Kondo demonstrated the potential suppressive activity of T-cells for the first time. The authors indicated that as well as enhancing the inflammatory response, T-cells also suppress them. Previously, it has been established that Treg expression is elevated by stimulation with Porphyromonas gingivalis antigens in periodontitis patients. Recent studies indicated that the number of Treg cells was significantly superior in chronic periodontitis lesions compared to gingivitis lesions., Cardoso et al. indicated that Tregs accumulate inside the periodontitis patients' gingiva and limit the effector immune responses and promote pathogen survival, which result in maintaining the chronicity of the disease. Furthermore, it has been reported that Treg infiltration could indicate an attempt to take tissue destruction under control but could also reflect a destructive role in periodontal disease.
IL-35, the newest part of IL-12 cytokine family, is produced by Treg cells and also from smooth muscle cells, microvascular endothelial cells, and monocytes.,,, It has been shown that IL-35 appears to play an immunomodulatory role in an extensive variety of disease circumstances., In an in vivo study, recombinant IL-35 injections protected laboratory mice against rheumatoid arthritis which is a chronic inflammatory disease, as is periodontitis.
In the present study, the GCFvol and IL-35 levels in SRP and SRP + laser groups decreased at all time points (1, 3, and 6 months) following the treatment, but reductions were statistically significant at 6 months compared to baseline. Broadly, IL-1 β/IL-35 ratio changed from 3/1 to 1/1 throughout the study. This finding may be explained by the rearrangement of cytokine balance from disease to health. According to our literature review, although very few papers were published regarding biocompatibility of IL-35 in gingival tissues and GCF, there is no published study comparing the effects of either Er, Cr: YSGG laser or SRP treatments on GCF IL-35 levels. Hence, we cannot compare our results with other studies, but our finding is in consistent with previous two studies. Kalburgi et al., Jin et al., and Kalburgi et al. demonstrated the expression of IL-35 mRNA in gingival tissues of chronic periodontitis, aggressive periodontitis, and healthy tissues and proved that IL-35 is related to the pathogenesis of periodontitis. Jin et al. indicated that IL-35 expression increases with CP development, which may help attenuate the process of chronic periodontitis.
| Conclusions|| |
As part of the present study results, as GCF IL-1 β/IL-35 ratio changed significantly from disease to health, we can suggest that IL-35 may be associated within the pathogenesis of periodontitis and that Er, Cr: YSGG laser can be used as an adjunct to SRP in periodontal treatment. Further longitudinal clinical, microbiological, and biochemical studies are required for the evaluation of the exact role of host mediated cytokine network in the pathogenesis of periodontal disease. In the future, identification of patients having high susceptibility sites for periodontal disease activities by diagnostic biochemical markers will possibly provide patient site-specific treatment methods.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Haffajee AD, Socransky SS. Microbial etiological agents of destructive periodontal diseases. Periodontol 2000 1994;5:78-111.
Research, Science and Therapy Committee of the American Academy of Periodontology. Treatment of plaque-induced gingivitis, chronic periodontitis, and other clinical conditions. J Periodontol 2001;72:1790-800.
Renvert S, Badersten A, Nilvéus R, Egelberg J. Healing after treatment of periodontal intraosseous defects. I. Comparative study of clinical methods. J Clin Periodontol 1981;8:387-99.
Lindhe J, Westfelt E, Nyman S, Socransky SS, Haffajee AD. Long-term effect of surgical/non-surgical treatment of periodontal disease. J Clin Periodontol 1984;11:448-58.
Stambaugh RV, Dragoo M, Smith DM, Carasali L. The limits of subgingival scaling. Int J Periodontics Restorative Dent 1981;1:30-41.
Crespi R, Barone A, Covani U. Histologic evaluation of three methods of periodontal root surface treatment in humans. J Periodontol 2005;76:476-81.
Polson AM, Frederick GT, Ladenheim S, Hanes PJ. The production of a root surface smear layer by instrumentation and its removal by citric acid. J Periodontol 1984;55:443-6.
Ando Y, Aoki A, Watanabe H, Ishikawa I. Bactericidal effect of erbium YAG laser on periodontopathic bacteria. Lasers Surg Med 1996;19:190-200.
Krause F, Braun A, Brede O, Eberhard J, Frentzen M, Jepsen S, et al.
Evaluation of selective calculus removal by a fluorescence feedback-controlled Er: YAG laser in vitro
. J Clin Periodontol 2007;34:66-71.
Myers TD. Lasers in dentistry. J Am Dent Assoc 1991;122:46-50.
Gutknecht N, Van Betteray C, Ozturan S, Vanweersch L, Franzen R. Laser supported reduction of specific microorganisms in the periodontal pocket with the aid of an Er, Cr: YSGG laser: A pilot study. ScientificWorldJournal 2015;2015:450258.
Hakki SS, Korkusuz P, Berk G, Dundar N, Saglam M, Bozkurt B, et al.
Comparison of Er, Cr: YSGG laser and hand instrumentation on the attachment of periodontal ligament fibroblasts to periodontally diseased root surfaces: An in vitro
study. J Periodontol 2010;81:1216-25.
Ting CC, Fukuda M, Watanabe T, Aoki T, Sanaoka A, Noguchi T, et al.
Effects of Er, Cr: YSGG laser irradiation on the root surface: Morphologic analysis and efficiency of calculus removal. J Periodontol 2007;78:2156-64.
Kinney JS, Morelli T, Oh M, Braun TM, Ramseier CA, Sugai JV, et al.
Crevicular fluid biomarkers and periodontal disease progression. J Clin Periodontol 2014;41:113-20.
Offenbacher S, Barros SP, Singer RE, Moss K, Williams RC, Beck JD, et al.
Periodontal disease at the biofilm-gingival interface. J Periodontol 2007;78:1911-25.
Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 1998;128:127-37.
Giannobile WV. Host-response therapeutics for periodontal diseases. J Periodontol 2008;79:1592-600.
Dewhirst FE, Stashenko PP, Mole JE, Tsurumachi T. Purification and partial sequence of human osteoclast-activating factor: Identity with interleukin 1 beta. J Immunol 1985;135:2562-8.
Gamonal J, Acevedo A, Bascones A, Jorge O, Silva A. Levels of interleukin-1 beta, -8, and -10 and RANTES in gingival crevicular fluid and cell populations in adult periodontitis patients and the effect of periodontal treatment. J Periodontol 2000;71:1535-45.
Vignali DA, Kuchroo VK. IL-12 family cytokines: Immunological playmakers. Nat Immunol 2012;13:722-8.
Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, et al.
The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007;450:566-9.
Collison LW, Chaturvedi V, Henderson AL, Giacomin PR, Guy C, Bankoti J, et al.
IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol 2010;11:1093-101.
Whitehead GS, Wilson RH, Nakano K, Burch LH, Nakano H, Cook DN, et al.
IL-35 production by inducible costimulator (ICOS)-positive regulatory T cells reverses established IL-17-dependent allergic airways disease. J Allergy Clin Immunol 2012;129:207-150.
Kuo J, Nardelli DT, Warner TF, Callister SM, Schell RF. Interleukin-35 enhances lyme arthritis in borrelia-vaccinated and -infected mice. Clin Vaccine Immunol 2011;18:1125-32.
Kalburgi NB, Muley A, Shivaprasad BM, Koregol AC. Expression profile of IL-35 mRNA in gingiva of chronic periodontitis and aggressive periodontitis patients: A semiquantitative RT-PCR study. Dis Markers 2013;35:819-23.
Köseoğlu S, Sağlam M, Pekbağrıyanık T, Savran L, Sütçü R. Level of interleukin-35 in gingival crevicular fluid, saliva, and plasma in periodontal disease and health. J Periodontol 2015;86:964-71.
Hakki SS, Berk G, Dundar N, Saglam M, Berk N. Effects of root planing procedures with hand instrument or erbium, chromium: yttrium-scandium-gallium-garnet laser irradiation on the root surfaces: A comparative scanning electron microscopy study. Lasers Med Sci 2010;25:345-53.
Crespi R, Capparè P, Toscanelli I, Gherlone E, Romanos GE. Effects of Er: YAG laser compared to ultrasonic scaler in periodontal treatment: A 2-year follow-up split-mouth clinical study. J Periodontol 2007;78:1195-200.
Dyer B, Sung EC. Minimally invasive periodontal treatment using the Er, Cr: YSGG laser. A 2-year retrospective preliminary clinical study. Open Dent J 2012;6:74-8.
Kelbauskiene S, Baseviciene N, Goharkhay K, Moritz A, Machiulskiene V. One-year clinical results of Er, Cr: YSGG laser application in addition to scaling and root planing in patients with early to moderate periodontitis. Lasers Med Sci 2011;26:445-52.
Qadri T, Poddani P, Javed F, Tunér J, Gustafsson A. A short-term evaluation of Nd: YAG laser as an adjunct to scaling and root planing in the treatment of periodontal inflammation. J Periodontol 2010;81:1161-6.
Miyazaki A, Yamaguchi T, Nishikata J, Okuda K, Suda S, Orima K, et al.
Effects of Nd: YAG and CO2 laser treatment and ultrasonic scaling on periodontal pockets of chronic periodontitis patients. J Periodontol 2003;74:175-80.
Saglam M, Kantarci A, Dundar N, Hakki SS. Clinical and biochemical effects of diode laser as an adjunct to nonsurgical treatment of chronic periodontitis: A randomized, controlled clinical trial. Lasers Med Sci 2014;29:37-46.
Eltas A, Orbak R. Effect of 1,064-nm Nd: YAG laser therapy on GCF IL-1β and MMP-8 levels in patients with chronic periodontitis. Lasers Med Sci 2012;27:543-50.
Gómez C, Domínguez A, García-Kass AI, García-Nuñez JA. Adjunctive Nd: YAG laser application in chronic periodontitis: Clinical, immunological, and microbiological aspects. Lasers Med Sci 2011;26:453-63.
Gershon RK, Kondo K. Cell interactions in the induction of tolerance: The role of thymic lymphocytes. Immunology 1970;18:723-37.
Aoyagi T, Yamazaki K, Kabasawa-Katoh Y, Nakajima T, Yamashita N, Yoshie H, et al.
Elevated CTLA-4 expression on CD4 T cells from periodontitis patients stimulated with Porphyromonas gingivalis
outer membrane antigen. Clin Exp Immunol 2000;119:280-6.
Cardoso CR, Garlet GP, Moreira AP, Júnior WM, Rossi MA, Silva JS, et al.
Characterization of CD4+CD25+ natural regulatory T cells in the inflammatory infiltrate of human chronic periodontitis. J Leukoc Biol 2008;84:311-8.
Nakajima T, Ueki-Maruyama K, Oda T, Ohsawa Y, Ito H, Seymour GJ, et al.
Regulatory T-cells infiltrate periodontal disease tissues. J Dent Res 2005;84:639-43.
Jin Y, Liu D, Lin X. IL-35 may maintain homeostasis of the immune microenvironment in periodontitis. Exp Ther Med 2017;14:5605-10.
[Table 1], [Table 2], [Table 3]