# Salivary Biomarkers of Inflammasome Activation in Unstable Periodontitis: A Case–Control Study

## TL;DR

This study found that specific biomarkers in saliva can indicate periodontal inflammation and suggest new treatment approaches for periodontitis.

## Contribution

The study identifies salivary biomarkers of inflammasome activation in unstable periodontitis and their correlations with disease severity.

## Key findings

- Salivary NLRP3, caspase-1, IL-1β, and IL-18 levels were significantly higher in unstable periodontitis patients.
- IL-37 was elevated in healthy individuals and showed anti-inflammatory correlations in periodontitis patients.
- IL-37 negatively correlates with pro-inflammatory cytokines, suggesting a regulatory role in periodontal inflammation.

## Abstract

The objective of this study was to investigate the complex network of inflammasome-related biomarkers (NOD-like receptor thermal protein domain associated protein 3 [NLRP3], caspase-1, interleukin [IL]-1β, IL-18, and IL-37) in unstable periodontitis by examining the salivary concentrations of these specific biomarkers and correlating them with periodontal parameters.

The design of this study was an observational case–control study. A salivary sample was collected from periodontally healthy patients (
n
 = 40) and unstable periodontitis patients (
n
 = 40). Full-mouth clinical periodontal parameters were recorded (plaque index, bleeding on probing, periodontal pocket depth, and clinical attachment loss). Enzyme-linked immunosorbent assay analyzed NLRP3, caspase-1, IL-1β, IL-18, and IL-37 salivary levels.

The normality of the data was tested using the Shapiro–Wilk test. Mean, standard deviation, and percentages were used for data description. An independent sample
t
-test, Mann–Whitney
U
test, and chi-square test were used to compare the two groups with a
p
-value of < 0.05. Spearman's correlation analysis was conducted to examine the relationships between variables.

In saliva samples, NLRP3, caspase-1, IL-1β, and IL-18 were the highest in the periodontitis group (
p
< 0.005), while IL-37 was highest in the healthy group (
p
< 0.005). There was significant (
p
< 0.012) negative weak correlation (−0.395) between IL-37 and IL-1β, and significant (
p
< 0.003) negative moderate correlation (−0.455) between IL-37 and IL-18 in the healthy group. A significant (0.031) positive weak correlation (0.342) was found between the salivary IL-37 and NLRP3, and a significant (
p
< 0.001) negative moderate correlation (−0.508) was found between salivary IL-37 and IL-1β, in the periodontitis group.

The NLRP3 inflammasomes and their cytokines (caspase-1, IL-1β, and IL-18) significantly promote periodontal inflammation and tissue destruction. In contrast, IL-37 acts as an anti-inflammatory cytokine, inhibiting the activity of the NLRP3 inflammasome and reducing excessive inflammation. This interplay highlights the potential of targeting NLRP3 and enhancing IL-37 as a therapeutic approach for the treatment of periodontal disease.