# The Interaction of Cytokines in Orthodontics: A Systematic Review
## 1 Introduction
In the saliva of patients treated with conventional lingual braces, the percentage of CD45+ (a marker for leukocytes) and CD326+ (a marker for epithelial cells) cells was higher, while the value of C-X-C motif chemokine ligand 9 (CXCL9) showed slightly higher secretion. These changes in chemokine secretion affect inflammatory actions and long-term oral health [71; 72]. photodynamic therapy (PDT), with the application of diode lasers at low-level wavelengths (LLLTs) from 660 and 830 nm, resulted in an improvement in the tooth element's rate displacement due to a higher concentration of IL-1\(\beta\), RANKL, and OPG present and a consequent increased osteocl activity [75; 76]. The average increase in orthodontic movement speed with the application of PDT, found in the various studies, is around 20%; calculated as a percentage of the control group in nine studies, it is 24% [77; 78]. PDT activates adenosine triphosphate (ATP) production, increases blood flow at the site, inhibits the secretion of inflammatory substances, and stimulates that of neurotransmitters, interfering with the conduction and stimulation of peripheral nerves, stimulating the release of endorphins [79]. Controlling the inflammatory state and pain of PDT, therefore, contributes, overall, to periodontal health in orthodontic patients [80; 81]. Cytokines are important biomarkers for health; they are small proteins released by different cells that influence the behavior of other cells by acting as messengers in the immune system. Cell signaling is crucial to the immune response, and dysfunction in this process is often associated with diseases such as cancer and autoimmune disorders. Cytokines are classified according to their properties and immune response. There are proinflammatory cytokines, which amplify inflammatory responses; growth factors, which promote cell survival and cause structural changes; and anti-inflammatory cytokines, which control the proinflammatory cytokine reaction. Several categories of cytokines perform specific functions in the immune system [82]. For example, chemokines are involved in the migration of immune system cells, interferons defend the body against viral and tumor diseases, and ILs mediate interactions between immune system cells [83]. Cytokines play crucial roles in modulating the immune response, inducing the inflammatory response, regulating hematopoiesis, and wound-healing. They are produced by various cells, including those of the immune system such as macrophages, B and T lymphocytes, and mast cells (Figure 2) [19]. Figure 2: Cytokines, mainly produced by cells of the immune system, but also by epithelial cells and fibroblasts (**A**), induce a biological response in other cells by activating membrane receptors and signal transduction mechanisms (**B**). Their short half-life in blood and extracellular fluids limits their range of action. The importance of cytokines in health and disease is evident in the processes of defense against infection, immune cell differentiation and responses, inflammation, sepsis, reproduction, viral pathogenesis, angiogenesis, and tumorigenesis [51]. Cytokines are also used in therapies, as natural immunositulants to combat immunodeficiencies such as in AIDS, or to reduce the side effects of chemotherapy in cancer treatment [84; 85]. It is, therefore, well understood that cytokines play a crucial role in orthodontic treatment, particularly in fixed orthodontics. They are fundamental in the regulation of inflammatory responses and bone remodeling, which are key processes during tooth movement. In-depth studies on the biological mechanisms of cytokines can improve the understanding of the initial phases of orthodontic treatment and any complications. Detailed knowledge of cytokines with more in-depth studies on biological mechanisms can lead to the identification of new therapeutic strategies, thus optimizing clinical outcomes and reducing treatment times. Therefore, the importance of cytokines in the orthodontic context cannot be underestimated.