# The Interaction of Cytokines in Orthodontics: A Systematic Review
## 4 Discussion
The study included 97 patients aged 13 to 18 years with Class I malocclusion. The collected saliva samples were analyzed by ELISA for vitamin D3 and IL-17A levels. The results revealed a significant decrease in mean salivary vitamin D3 levels from early to late phase and a subsequent stabilization in the log phase. At the same time, salivary levels of IL-17A showed a decrease from early to late phase and a further decrease in the log phase. A comparison of vitamin D3 levels between genders showed no significant differences, contrary to some previous studies potentially influenced by demographic variations [91]. The descriptive-analytical study by [PERSON] et al. investigates the dynamics of IL-8 levels in GCF during OT. The research involved 20 orthodontic patients, including 10 adolescents (under 19 years old) and 10 adults (19 years and older). Inclusion criteria ensured good general health, no recent antibiotic or anti-inflammatory use, no periodontal disease, Class I malocclusion, permanent dentition, and no planned dental extraction. GCF samples were collected at different times: before OT and 24 h, 7 days, and 28 days after the start of treatment. IL-8 levels were measured by an ELISA method. The study revealed that IL-8 concentration significantly decreased one day after treatment compared to baseline, followed by an increase at one and four weeks after treatment, but did not reach baseline. Interestingly, the age groups (adolescents and adults) showed a significant difference in IL-8 concentration on the first day of treatment, with adults showing lower IL-8 levels. No significant difference was observed between the sexes during the treatment period [92]. The prospective clinical study by [PERSON] et al. investigates the dynamics of RANKL concentrations in GCF during the initial stages of OT, specifically comparing the effects of Passive SL (Damon Q; Ormco) and PEA (MBT; Ormco) bracket systems. Patients, aged 15 to 35 years, were divided into two experimental groups and a control group. RANKL concentrations were analyzed by ELISA. The results revealed statistically significant differences in RANKL concentrations within the experimental groups, particularly in the passive SL group. Additionally, the study explored the impact of bracket systems on tooth movement and RANKL expression [18]. The passive SL bracket system showed higher RANKL concentrations at 168 h than the PEA system, attributed to different force systems and mechanotherapeutic aspects. This suggests a potential association between bracket systems, force application, and RANKL production during the early stages of OT. Understanding the nuanced responses of RANKL concentrations in the GCF to different bracket systems improves our understanding of orthodontic mechanotherapy, guiding clinicians in choosing bracket systems that are appropriate for patients' needs. Further investigations with extended follow-up periods and diverse patient populations are needed to corroborate and generalize these findings [93]. [PERSON] et al. aimed to investigate the chemokine levels in 40 saliva samples from patients treated with conventional lingual and labial fixed orthodontic appliances. Specifically, salivary chemokine secretion showed uniqueness between the lingual and labial appliance groups. CXCL8, CCL11, CCL2 and CCL5 showed higher secretion in subjects with labial braces, while CXCL9 showed slightly higher secretion in subjects with lingual braces. These variations in chemokine secretion suggest different impacts on the oral microenvironment, influencing inflammatory actions and long-term oral health [72]. The study by [PERSON] et al. analyzed the impact of OT with lingual and labial fixed appliances on salivary cytokine levels in a cohort of 40 patients. The saliva samples comprised 20 from patients with traditional lingual appliances and 20 from those with labial fixed appliances.