# The Interaction of Cytokines in Orthodontics: A Systematic Review
## 4 Discussion  
The production of specific cytokines in the laboratory is an area of active research. Applying a force of a certain magnitude, frequency, and duration to the teeth enables orthodontic tooth movement to the periodontal ligament, causing alveolar bone and pe  
Figure 4: Bias assessment by Robins tool. [PERSON] et al. (2017) [85], [PERSON] al. (2012) [18], [PERSON] et al. (2019) [86], [PERSON] et al. (2021) [31], [PERSON] et al. (2021) [87], [PERSON] et al. (2022) [88], [PERSON] et al. (2015) [19], [PERSON] et al. (2018) [89], [PERSON] et al. (2022) [90], [PERSON] (2023) [91], [PERSON] et al. (2021) [92], [PERSON] et al. (2018) [93] [PERSON] et al. (2021) [72], [PERSON] et al. (2021) [71], [PERSON] et al. (2015) [69], [PERSON] et al. (2018) [94], [PERSON] et al. (2018) [62], [PERSON] et al. (2019) [95]. riodontal ligament remodeling. Orthodontic tooth movement is preceded by an acute inflammatory response, characterized by vascular dilatation and increased vascular permeability. It is not only interesting to understand which and how many proinflammatory cytokines are activated and released, but also to understand the various types of braces used and the various orthodontic movements sought [96]. In order to do so, [PERSON] et al. evaluated the impact of RME on periodontal health, specifically examining markers of oxidative stress and IL-1\(\beta\) levels in GCF. A modified hyrax appliance was used for OT, and patients were monitored at various times, including activation and maintenance periods. Clinical parameters, including probing depth, gingival index, plaque index and bleeding on probing, were recorded throughout the duration of the study [89]. GCF samples were collected, and markers of oxidative stress (total antioxidant capacity (TAC), total oxidant state (TOS), oxidative stress index (OSI)) and IL-1\(\beta\) levels were measured. In addition, nitric oxide (NO) activity was evaluated. The results indicated that RME had no adverse effects on periodontal tissues. The probing depth increased during the early stages but remained stable thereafter. GCF volume increased significantly during RME, attributed to mechanical trauma during device activation. IL-1\(\beta\) levels showed an insignificant increase during RME, probably due to the minimal orthodontic forces applied. NO levels increased during RME, with higher values associated with force loading and sutural relapse in the retention period. TAC and TOS levels in GCF varied between the buccal and palatal sides, with higher palatal levels. The study concludes that RME had no adverse effects on periodontal tissues, and that the observed changes in oxidative status and IL-1\(\beta\) levels can be explained by the orthopedic effect of applied forces [89]. Meanwhile, [PERSON] et al. explored the molecular and clinical complexities of passive OT by focusing on 20 patients who presented with indications for interceptive OT, had an anterior open bite, and maintained good oral hygiene and periodontal health. Exclusion criteria included systemic diseases, recent use of antibiotics or anti-inflammatory drugs, bleeding during GCF sampling, and presence of orthodontic accessories. The levels of cytokines--IL-8, IL-1\(\beta\), IL-6, IL-10, TNF-\(\alpha\) and IL-12p70--in the GCF were measured. Spurs were bonded to the lingual surface of mandibular incisors, and GCF samples were collected from maxillary and mandibular central incisors at baseline, 24 h and 7 days after bonding. Notably, an increase in GCF cytokines was observed as early as between 1 min and 1 h after bonding, reaching a peak at 24 h, followed by a secondary peak at day 7. The study offers a unique insight into the molecular dynamics of ILs during passive OT in children, highlighting the influence of lip pressure and perioral musculature on tooth movement and open-bite correction [90]. [PERSON]'s study aimed to assess salivary levels of vitamin D3 and the pro-inflammatory cytokine IL-17A in patients receiving fixed orthodontic therapy.