# The Interaction of Cytokines in Orthodontics: A Systematic Review
## 4 Discussion
The analysis focused on a panel of 13 cytokines, including IL-4, IL-2, CXCL10, IL-1\(\beta\), IL-17A, IL-6, IL-10, TNF-\(\alpha\), CCL2, IFN-\(\gamma\), IL-12p70, CXCL8, and TGF-61 [72; 97]. The results revealed significantly higher levels of CCL2, IL-17A, and IL-6 in patients with lingual braces compared with those with fixed labial braces. In addition, ELISA tests demonstrated lower levels of defenins (HNP-1, HNP-2, HBD-1, and HBD-2) in the saliva of patients with lingual braces. The results suggest that OT with lingual braces induces a distinct inflammatory response, as evidenced by the altered levels of cytokines and cellular composition in saliva. Despite the limitations of the study, including the relatively small sample size, these results provide valuable insights into the potential long-term effects of orthodontic appliances on oral health and tissue homeostasis. Further research is needed to elucidate the underlying signaling pathways and optimize orthodontic appliances to improve patient outcomes [71]. A study by [PERSON] et al. analyzed the levels of IL-17A and RANKL in the GCF of adolescents and young adults undergoing OT. The study aimed to analyze the impact of treatment duration on cytokine expression and to assess changes by gender. Participants were divided into two groups: Group A (treatment group) with fixed braces and Group B (control group) without braces. GCF samples were collected from the mesial, medial and distal sides of the right maxillary canine, and IL-17A and RANKL levels were measured by an ELISA. The results indicated a significant increase in IL-17A and RANKL levels in the treatment group compared with controls. In addition, gender-specific differences were observed, with males showing higher cytokine expression than females. The correlation between IL-17A and RANKL suggested a synergistic effect. The results underscore the impact of OT on inflammatory processes, osteoclast, and OTM. The study emphasizes the importance of considering patients' sex and hormone levels in treatment planning, as women with higher estrogen levels showed lower cytokine expression and potentially slower OTM [69]. In a study by [PERSON] et al., the GCF of 18 patients, before and after OT with passive self-ligating brackets and pre-ligated brackets, was examined. Tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)) concentrations were measured at different time points using ELISA kits. The results showed significant differences in TNF-\(\alpha\) values between the experimental groups (self-ligating brackets and passive elastomeric ligature) and control groups after orthodontic force application. TNF-\(\alpha\) levels increased at 24 h in both experimental groups, decreasing significantly after 168 h in the passive elastomeric ligature group. In contrast, levels remained elevated in the self-bonded bracket group, suggesting different inflammatory responses. The study provides insights into the dynamic changes in TNF-\(\alpha\) during early orthodontic tooth movements and highlights the potential implications of bracket systems on inflammatory responses. These findings contribute to the understanding of cytokine involvement in bone remodeling during OT [94]. In a retrospective clinical study by [PERSON] et al., the correlation between inflammatory cytokine levels in saliva and the development of white spot lesions (WSL) following invisible orthodontic correction was explored. Saliva samples were collected at three distinct time intervals: before the placement of orthodontic appliances (T0), 6 months after placement (T1), and during follow-up evaluations. Analysis revealed significant differences in the transcript levels of various inflammation-related cytokines, including CXCL1, CXCL2, CXCL8, IL-1\(\beta\), IL-2, CCL3, and CCL4, between patients with WSL (WLG) and those without (nWLG). Further investigation showed that after treatment, the levels of CXCL8, CCL3, CCL4, IL-1\(\beta\) and IL-2 in saliva increased significantly in both groups.