Interleukin-34 in Stage I and II Periodontitis

The Effect of Non-Surgical Periodontal Therapy on Interleukin-34 in Stage I and II Periodontitis (A Controlled Clinical Trial With Biochemical Analysis)

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).

Study Overview

• Status: Completed
• Conditions: Cytokine Storm
• Intervention / Treatment: Procedure: Non-Surgical periodontal therapy

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

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Faculty of Dentistry-Ain shams university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with stage I and II grade B Periodontitis in addition to periodontally healthy individuals.
• Both genders aged from 20-50 years
• Minimum 20 natural teeth excluding third molars.
• Good compliance with the plaque control instructions following initial therapy.
• Availability for follow-up and maintenance program.

Exclusion Criteria:

• Smokers.
• Pregnant and lactating females.
• Systemic diseases that could affect the outcome of the therapy (According to the Cornell Medical Index-Health Questionnaire).
• Patients taking antibiotics, anti-inflammatory drugs, and immunosuppressive therapy during the preceding 6 months before the start of the trial and during the study.
• Patients who have undergone any periodontal therapy in the last 6 months.
• Vulnerable groups of patients' e.g. (handicapped patients).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Stage I grade B periodontitis patients; 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 maintenance visits were given to them.	Procedure: Non-Surgical periodontal therapy; Supra and Subgingival debridement for all patients except periodontally healthy individuals
Active Comparator: Stage II grade B periodontitis patients; 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 maintenance visits were given to them.	Procedure: Non-Surgical periodontal therapy; Supra and Subgingival debridement for all patients except periodontally healthy individuals
No Intervention: Periodontally healthy individuals; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the IL - 34 levels in GCF before &after NSPT of stage I and II grade B periodontitis patients in comparison to periodontally healthy individuals	To measure the IL - 34 levels in ng/L before &after NSPT of stage I and II grade B periodontitis patients in comparison to periodontally healthy individuals	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate probing depth before & after NSPT in Stage I and II grade B periodontitis	To evaluate probing depth (in mm) before & after NSPT in Stage I and II grade B periodontitis	3 months
To evaluate Clinical attachment Level before & after NSPT in Stage I and II grade B periodontitis	To evaluate Clinical attachment Level (in mm) before & after NSPT in Stage I and II grade B periodontitis	3 months
To evaluate Plaque index before & after NSPT in Stage I and II grade B periodontitis patients	To evaluate Plaque index (0 score indicated zero plaque to 3 score that indicated highest plaque index score) before & after NSPT in Stage I and II grade B periodontitis patients	3 months
To evaluate Gingival index before & after NSPT in Stage I and II grade B periodontitis patients	To evaluate Gingival index (0 score indicated no bleeding to 3 score that indicated excessive bleeding ) before & after NSPT in Stage I and II grade B periodontitis	3 months

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Study Director: hala A. Abuel Ela, Professor, Professor of Oral Medicine, Periodontology, Oral Diagnosis, Faculty of Dentistry, ASU; Study Chair: Doaa Adel-Khattab, Asso.Prof., Associate Prof. of oral medicine, Periodontology and Oral diagnosis Faculty of dentistry ASU

Publications and helpful links

Helpful Links

• Serum cytokine levels in periodontitis patients in relation to the bacterial load
• Gingival Crevicular Fluid (GCF): A Diagnostic Tool for the Detection of Periodontal Health and Diseases
• Emerging roles of Interleukin-34 together with receptor activator of nuclear factor-kB ligand and
• Tooth loss in complying and non-complying periodontitis patients with different periodontal risk levels during supportive periodontal care
• Diagnostic potential and future directions of biomarkers in gingival crevicular fluid and saliva of periodontal diseases: Review of the current evidence
• Effect of nonsurgical periodontal therapy on interleukin-34 levels in periodontal health and disease
• Periodontitis: A Multifaceted Disease of Tooth-Supporting Tissues
• Discovery of a cytokine and its receptor by functional screening of the extracellular proteome
• Levels of myeloid-related proteins in saliva for screening and monitoring of periodontal disease
• Salivary Colony Stimulating Factor-1 and Interleukin-34 in Periodontal Disease
• Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions
• Staging and grading of periodontitis: Framework and proposal of a new classification and case definition
• Cytokines, inflammation, and pain

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Actual): July 1, 2023
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: September 19, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 25, 2023

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 24, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Shock; Periodontitis; Cytokine Release Syndrome
• Other Study ID Numbers: FDASU-Rec IR 092303

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No