Periodontitis is characterized by a microbiota-induced inflammation that triggers the host immune response causing the release of inflammatory mediators and cytokines which are secreted by different types of cells, such as fibroblasts, macrophages, and lymphocytes, especially during the active phases of periodontitis causing periodontal breakdown. Cytokines also act as the first wave of responses against pathogens and stimuli at barrier sites and connect tissue cells with lymphocytes and accessory cell populations [16].
CSF-1 and IL-34 are examples of cytokines that are important in regulating the survival, proliferation, and differentiation of mononuclear phagocytes. In an in vivo study in a rat model, inhibition of the CSF-1 receptor by IL-34 had been shown to reduce alveolar bone loss in periodontal tissue, it was concluded that IL-34 plays an important role in RANKL-induced osteoclastogenesis and highlighted their role in periodontal pathology [6].
Although a few clinical studies have examined the relationship between IL-34 and periodontitis, these studies have given conflicting results regarding the IL-34 levels in periodontal health and disease. Boström & Lundberg in 2013 [17] concluded that primary human gingival fibroblast expresses IL-34 and pro-inflammatory cytokines such as IL-1β and TNF-α increase the levels of IL-34 mRNA in the inflamed connective gingival tissue in periodontitis lesions which indicate that IL-34 may be involved in the complex pathogenesis of periodontitis. It was revealed that the level of IL-34 mRNA expression in periapical lesions was significantly higher than that of the normal control so it was concluded that IL‑34 may be closely related to inflammation of chronic apical periodontitis [18]. On the other hand, some studies sdetected lower salivary levels of IL-34 in patients with periodontal disease. Therefore, they suggested that IL-34 might have a protective role in the pathogenesis of periodontal disease. Therefore, this study was to detect the role of IL-34 in periodontal disease and to assess the effect of NSPT on its level in GCF) [9, 10].
The results of the present study demonstrated that IL-34 GCF level was higher in stage II grade B periodontitis patients than in stage I grade B periodontitis patients and periodontally healthy individuals, this can be attributed to the pro-inflammatory properties of tumor necrosis factor-alpha (TNF‑α) and interleukin-1 beta (IL‑1β) which regulate IL‑34 expression in gingival fibroblasts, by a mechanism involving nuclear factor kappa B (NF-κB) and Mitogen-activated protein kinase (MAPK).[17]
Moreover, these results agreed with Guruprasad and Paradeep (2018) [7] who concluded that the mean of IL‑34 concentration in GCF and plasma was statistically higher in generalized chronic periodontitis patients (p ≤ 0.05) compared to periodontally healthy individuals. It was concluded that IL 34 was found to be statistically higher in GCF of aggressive and chronic periodontitis patients compared to periodontally healthy individuals [19]. More recently in 2023, Luo et al. [20] found that IL-34 level was prominently increased in chronic periodontitis patients compared to healthy participants and these results were consistent with the current study.
The current study also assessed the effect of NSPT on IL-34 levels in periodontitis groups and found that GCF IL-34 level was higher in both periodontitis groups compared to periodontally healthy individuals. In accordance with our study, Guruprasad and Pradeep (2018) [7], studied the effect of NSPT on IL‑34 levels in GCF and plasma and concluded the decrease in levels of IL-34 after 8 weeks from NSPT in chronic generalized periodontitis patients. Bozkurt Doğan et al. (2021) [8], studied GCF IL-34 levels in patients with stage III-grade B periodontitis patients pre- and 6 weeks post-NSPT, and it was concluded that GCF IL-34 levels decreased after NSPT. In addition, Luo et al. (2023) [20] concluded that the expression levels of IL-34 were decreased in chronic periodontitis patients after 1 year from NSPT.
Although, there was a significant reduction in the level of IL-34 in GCF in both groups in the current study after NSPT, still the level of IL-34 was higher in stage II periodontitis patients compared to stage I grade B periodontitis patients and periodontally healthy individuals, but the results were statistically insignificant. These results were consistent with a study that detected the total concentration of GCF IL-34 levels was found greater in the stage III-grade C group than in the stage II-grade B group at baseline and after NSPT (P < 0.05) [8].
Spearman rank order correlation coefficient demonstrated a positive correlation between clinical parameters (PD and CAL) and IL 34 levels in GCF in periodontitis groups which was statistically significant. This result was consistent with study that reported that high levels of IL-34 in GCF in patients with chronic and aggressive periodontitis were positively correlated with PI, GI, PPD, and CAL [19]. In addition, Bozkurt Doğan et al. (2021) [8] found a significantly positive correlation between IL-34 level, RANKL/OPG ratio levels, CAL, and GI in stage III grade B periodontitis patients (P < 0.05).
The current study also assessed the ability of IL-34 to distinguish periodontitis patients from healthy participants as it exhibited a good ability to discriminate between periodontitis and health. This result was consistent with a study by Lira-Junior et al. (2021) [10] that reported that IL-34 exhibited moderate performance in distinguishing periodontitis patients from healthy participants, with AUC varying from 0.67 to 0.74.
In contrast, a study conducted by Martinez et al. (2017) [9] found that levels of IL-34 in saliva were lower in patients with gingivitis and periodontitis compared to healthy patients. These lower levels were also found to be negatively correlated with clinical indicators of inflammation and disease severity; this suggests that IL-34 may play a role in maintaining periodontal health. Another study concluded that the level of IL-34 in saliva was significantly lower in periodontitis compared to both healthy individuals and gingivitis patients and found negative correlation to the clinical parameters, in addition to an increase in IL-34 levels significantly 3 months after treatment [10], these previous studies were inconsistent with the current study. The difference in results can be attributed to the examination of markers from different fluids and differences in the degree of periodontitis.
The limitation of this current study was short follow-up. Furthermore, patients with different stages and grades of periodontitis are recommended to further explore the effect of IL-34 on periodontitis.