# The Interaction of Cytokines in Orthodontics: A Systematic Review
## 4 Discussion
Importantly, the WLG group showed significantly higher levels of these inflammatory cytokines than the nWLG group. These results underscore the significant role of inflammatory cytokines, particularly CXCL8, in the development of white spot lesions after OT with clear aligners in adolescents. The study suggests that monitoring and understanding the levels of these cytokines could serve as a valuable indicator to predict and prevent WSLs, helping to improve post-treatment outcomes in orthodontic patients [98]. [PERSON] et al. studied the efficacy of glucosamine sulfate (GS) and hyaluronic acid (HA) in the treatment of osteoarthritis of the temporomandibular joint (OA). The GS + HA intervention involved intra-articular injection of sodium HA and GS hydrochloride tablets, while the control group received a placebo. Clinical outcomes, such as TMJ pain and maximum mouth opening, as well as laboratory results measuring proinflammatory cytokines in TMJ synovial fluid, were evaluated. The results of short- and long-term efficacy analysis indicated that both GS and HA injections alone were effective in relieving TMJ OA symptoms. The GS group showed significant improvements in pain relief, mouth opening, and reduction in proinflammatory cytokines compared with the placebo group, especially in the long term. Age-related differences were observed: younger patients had better short-term results, while both age groups showed similar long-term improvements. The study suggests that GS, in addition to HA injection, may have an impact on inflammation-associated cytokines, providing a potential therapeutic approach for TMJ OA patients [99]. This research underscores the importance of employing multiple approaches to managing orthodontic pain. While medications, like naproxen, can effectively control pain, it is also essential to consider psychological factors, such as anxiety and catastrophizing, that influence pain perception. In addition, the comparison between drugs and nonpharmacological therapies, such as LLLT, highlights the need for a personalized approach to optimize orthodontic pain management. Further research should explore more specific biological markers and deepen understanding of the underlying mechanisms of orthodontic pain to improve treatment strategies. A study conducted by [PERSON] et al. extensively examined the impact of orthodontic brackets, focusing on the difference between self-ligating brackets and conventional brackets. The interesting finding concerns changes in cytokine levels and bacterial accumulation in GCF. The identification of increased TNF-\(\alpha\) levels and increased bacterial presence in self-ligating brackets is a remarkable finding. These findings suggest that the choice of bracket type could influence the inflammatory response and the risk of bacterial accumulation. However, it is crucial to note that further research on larger samples and a focus on various orthodontic movements is needed to confirm and further investigate these findings [62]. [PERSON] et al. addressed issues related to the application of surface sealants, which are common during OT with fixed appliances. The main concern was the possible toxicity of monomers in resin-based sealants and their ability to cause inflammatory and immune responses [95]. A study by [PERSON] et al., 2017, aimed to detect and quantify cytokine levels in GCF during OT [85]. The study sample included 15 healthy patients who underwent OT. Periodontal monitoring was performed at each stage of OT, with assessments of visible plaque and bleeding on palpation. In addition, GCF samples were collected from specific teeth at different stages of OT using Luminex technology. Cytokine levels remained constant during orthodontic movement, suggesting a constant response to mechanical stimulus. Cytokines, proteins involved in inflammation, play a crucial role in biological processes associated with orthodontic tooth movement.