Retinoic Acid Therapy and Regulation of Salivary and Serum IL-1β, IL-8 and MCP-1 Levels

Effect of Systemic Retinoic Acid Use on Periodontium-Related T Cell Differentiation

This prospective cohort study analysed the effects of systemic retinoic acid use on periodontal status, salivary flow rate (SFR), and salivary and serum levels of interleukin (IL)-1β, IL-8 and monocyte chemoattractant protein (MCP)-1.

Study Overview

• Status: Completed
• Conditions: Acne Vulgaris; Gingivitis and Periodontal Diseases; Inflammation Biomarkers; Saliva Collection; Vitamin a

Detailed Description

Vitamin A (isotretinoin, 13-cis-retinoic acid) and its metabolites are essential for various biological processes, including vision, development, and immune regulation. The periodontium, which consists of tissues supporting the teeth, can transition from health to disease due to multiple factors. The impact of retinoic acid (RA) on periodontal tissues has primarily been investigated in vitro; however, evidence suggests that it may reduce alveolar bone destruction and modulate cytokine expression, indicating potential anti-inflammatory properties. Nevertheless, there is a lack of studies examining the relationship between RA and periodontal health.

This study aims to evaluate the potential association between systemic RA use and the periodontal tissue response in terms of inflammatory markers (cytokines: IL-1β, IL-8; chemokines: MCP-1) and to assess dental/periodontal status at different time intervals. The study hypothesizes that RA use will enhance the periodontal tissue response independently of the existing bacterial biofilm and its quantity in the oral cavity, thereby negatively affecting the maintenance of periodontal health through alterations in the periodontium's defense mechanisms.

Saliva and serum samples from 24 participants were collected to assess inflammatory responses. The samples were obtained and stored at Istanbul Medipol University Mega Hospital, Turkey, and subsequently transferred to the University of Turku, Finland, for laboratory analyses. Serum and saliva samples were analyzed for inflammatory markers (IL-1β, IL-8, MCP-1) using multiplex immunoassay kits (Millipore; MILLIPLEX® Human Cytokine/Chemokine/Growth Factor Panel A-Immunology Multiplex Assay, #HCYTA-60K, Merck Millipore, Massachusetts, MA). Additionally, sociodemographic, dental, and periodontal data of each participant were analyzed.

This study will contribute to understanding the potential relationship between RA and periodontal status, as well as the effects of RA on the inflammatory response of periodontal tissues.

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey
    • Medipol University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patient recruitment, data collection, and sample acquisition were conducted at Istanbul Medipol University, Faculty of Dentistry, and Istanbul Medipol University Mega Hospital, Dermatology Clinic, Turkey, between September 2023 and July 2024.

Description

Inclusion Criteria:

1. Directed to use isotretinoin 0,5 to 1 mg/kg/day for 6 months for the treatment of moderate and severe acne vulgaris or nodular acne according to the global acne rating by dermatologist
2. Being at the age range of 18-30 years old
3. Willing to participate to the study
4. Periodontally Healthy

Exclusion Criteria:

1. Systemic diseases other than acne vulgaris or nodular acne
2. Use of antibiotics, anti-inflammatory drugs, nonsteroidal anti-inflammatory drugs, steroids, immunosuppressants, beta-blockers, calcium channel blockers, anticoagulants, or hormonal contraceptives within 6 months prior to the initiation of the study
3. Pregnancy or being lactating
4. Excessive use of alcohol
5. Smoking
6. Received nonsurgical periodontal therapy during preceding 6 months or surgical periodontal therapy during preceding 12 months
7. Have fewer than 20 natural teeth excluding third molars
8. Have orthodontic appliances.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
retinoic acid users; A total of 24 periodontally healthy participants who were prescribed isotretinoin (Retinoic acid) (0.5-1 mg/kg/day) for six months to treat moderate to severe acne vulgaris or nodular acne, based on the Global Acne Grading System, were included in the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bleeding on probing	To assess the inflammatory status of the pocket base and pocket epithelium, bleeding was recorded 30 seconds after probing depth measurement. The presence of bleeding was scored as positive (+), while the absence of bleeding was recorded as negative (-). The percentage value of the Bleeding on Probing for each patient was calculated using the following formula: (Number of bleeding surfaces / Total number of tooth surfaces) × 100	at 4 time point: before retinoic acid treatment, during(6th week and 5th month) retinoic acid treatment and 2nd month after completion of retinoic acid therapy
IL-1beta, IL-8 and MCP-1 levels	Interleukin(IL)-1beta, IL-8 and monocyte chemoattractant protein (MCP)-1 are inflammatory cytokines which show inflamatory changes.	at 4 time point: before retinoic acid treatment, during(6th week and 5th month) retinoic acid treatment and 2nd month after completion of retinoic acid therapy
salivary flow rate	Salivary flow rate was calculated by the collected saliva volume SFR=Volume of saliva (mL) collected in 10 minutes/10 minutes.	at 4 time point: before retinoic acid treatment, during(6th week and 5th month) retinoic acid treatment and 2nd month after completion of retinoic acid therapy

Collaborators and Investigators

• Sponsor: Medipol University

Publications and helpful links

General Publications

• Atalay N, Balci N, Toygar HU, Yardimci G, Gursoy UK. Serum, saliva, and gingival tissue human beta-defensin levels in relation to retinoic acid use. J Periodontol. 2023 May;94(5):597-605. doi: 10.1002/JPER.22-0466. Epub 2022 Dec 19.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: inflammation; saliva; chemokines; periodontal health; retinoic acid
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Infections; Skin Diseases; Gingival Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Inflammation; Acne Vulgaris; Periodontal Diseases; Gingivitis
• Other Study ID Numbers: 1108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No