Interleukin-34 in Stage I and II Periodontitis
Condition: Cytokine Storm
MeSH terms: Periodontitis; Cytokine Release Syndrome
Study type: Interventional

Summary: 
      Interleukin 34 (IL-34) is the second active component of (colony-stimulating factor receptor)
      CSF-1R. With regards to periodontal disease, It is debatable whether IL-34 is a
      pro-inflammatory cytokine (as seen in rheumatic arthritis and Sjogren syndrome) or an
      anti-inflammatory cytokine( as seen in Alzheimer's disease) so further studies could be
      conducted to better understand whether IL-34 is a proinflammatory or anti-inflammatory
      cytokine in the pathogenesis of periodontal diseases and to evaluate the change of its levels
      in Gingival crevicular fluid (GCF) in patients with periodontal disease after non-surgical
      periodontal therapy (NSPT).
    

Detailed description: 
      Periodontal disease is a multifactorial infection induced by a complex of bacterial species
      that interact with host tissues and cause destruction of the periodontal structures,
      including the supporting tissues of the teeth, alveolar bone, and periodontal ligament.

      The bacterial biofilm formation initiates gingival inflammation; however, periodontitis
      initiation and progression depend on dysbiotic ecological changes in the microbiome in
      response to nutrients from gingival inflammatory and tissue breakdown products that enrich
      some species and anti-bacterial mechanisms that attempt to contain the microbial challenge
      within the gingival sulcus area once the inflammation has initiated.

      Current evidence supports multifactorial disease influences, such as smoking, diabetes
      mellitus, obesity, metabolic syndrome, osteoporosis, low dietary calcium and vitamin D and
      other immunoinflammatory responses that make the dysbiotic microbiome changes more likely for
      some patients than others and likely influence the severity of disease for such individuals.

      During periodontitis, the pathogen triggers the white blood cells of the innate immune system
      to release proinflammatory mediators such as cytokines that play a vital role in the
      progression of the inflammation process of periodontitis. In addition, these pathogens can
      activate the acquired immune system contributing to the release of more cytokines and
      chemokines that cause permanent bone damage and irreversible periodontal attachment loss.

      Cytokines are defined as soluble small proteins (~5-20 kDa) that bind to specific receptors
      on certain cells, stimulate some internal cellular changes, and cause multiple genetic and
      chemical regulations.

      There are two different types of inflammatory cytokines: proinflammatory cytokines that are
      involved in inflammatory reactions including interleukin-1 beta (IL-1β), interleukin-6
      (IL-6), interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-α), and anti-inflammatory
      cytokines that regulate or control the pro-inflammatory cytokine response including
      interleukin-4 (IL-4), interleukin-1 receptor antagonist (IL-1RA) and interleukin-10 (IL-10).

      NSPT aimed at the mechanical removal of bacterial plaque from the tooth surface is considered
      the "gold standard." This procedure decreases the number of Gram-negative bacteria in favor
      of Gram-positive bacteria as well as reduces the overall number of microorganisms in
      periodontal pockets and decreases the amount of proinflammatory cytokines.

      Recent methods in oral and periodontal disease diagnostic research are identifying
      periodontal risk which is quantified by objective measures like biomarkers which are
      diagnostic tools to measure periodontal disease at the molecular, cellular, tissue, and
      clinical levels. The biological media for detecting periodontal disease biomarkers include
      GCF, saliva, serum, subgingival plaque, and tissue biopsies.

      The major attraction of GCF as a diagnostic marker is the site-specific nature of the sample
      which may offer the basis for patient-specific diagnostic tests for periodontal disease.
      Moreover, the simplicity of its use along with a level of reliability and low cost favors its
      use over other modalities.

      The discovery of new biomarkers will aid in the development of new therapeutic approaches via
      host modulatory drugs for periodontal disease treatment leading to more individualized,
      targeted treatments for oral health.

      In 2008, Lin identified a secreted protein known as IL-34 with a high functional selectivity
      represented by stimulating monocyte survival in a CSF-1R-dependent manner. Many studies
      provided insight into IL-34 biology, but many questions remain unanswered, specifically in
      terms of its function.

      High expression of IL-34 correlates with disease severity in autoimmune diseases (Sjögren's
      syndrome, SLE, and RA), and inflammatory diseases (liver fibrosis, kidney disease, and
      inflammatory bowel disease). In contrast, IL-34 plays a protective role in some diseases,
      such as atopic dermatitis, Alzheimer's disease, breast cancer, and head and neck cancer.

      In periodontal disease, some studies such as Guruprasad & Pradeep in 2018 and Bozkurt Doğan
      in 2021 suggested that IL-34 is a proinflammatory cytokine in the pathogenesis of periodontal
      disease while others such as Martinez in 2017 and Lira-Junior in 2021 concluded that IL-34
      play a protective role in periodontal disease.

      Therefore, Further studies must be carried out to confirm these findings and to better
      understand the possible role of IL-34 in the pathogenesis of periodontal diseases and to
      evaluate its levels in GCF in patients with periodontal disease after NSPT
    

Intervention name(s): Non-Surgical periodontal therapy
Intervention type(s): Procedure
Intervention description(s): Supra and Subgingival debridement for all patients except periodontally healthy individuals
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Nonsurgical periodontal debridement was performed on patients using an ultrasonic scaler and universal curettes (2R - 2L and 4R- 4L). Oral Hygiene measures were instructed following treatment and follow-up after 3 months.
Masking: None (Open Label)
Primary purpose: Treatment