The effect of smoking on macrophage polarization in the pathogenesis of periodontitis

ABSTRACT The Effect of Smoking on Macrophage Polarization in the Pathogenesis of Periodontitis Aim: Although studies exist on the relationship between periodontitis and smoking, research directly examining the effect of smoking on macrophage polarization in the pathogenesis of periodontitis is limited. Therefore, the aim of this study is to determine the direction of macrophage polarization in periodontal tissues in smokers and to reveal the direction of the inflammatory response in macrophage polarization (M1, M2) in smokers. Materials and methods: In the study, a total of 80 systemically healthy individuals were evaluated in four groups according to smoking status and periodontal health status (non-smoking healthy, non-smoking periodontitis, smoking healthy, and smoking periodontitis; n=20 in each group). Clinical evaluation measured plaque index, gingival index, bleeding on probing (%), pocket depth, and clinical attachment loss. Arginase (Arg)-1 and inducible nitric oxide synthase (iNOS) protein levels in gingival tissue samples obtained from participants were analyzed using the enzyme-linked immunosorbent assay (ELISA) method. The effects of independent factors on patient groups were examined using multinomial logistic regression analysis. The effects of independent factors on periodontitis were examined using Binary Logistic Regression Analysis. The effect of the examined parameters on distinguishing periodontitis was evaluated using ROC analysis. The Monte Carlo Corrected Fisher's Exact Test was used to examine the relationship between categorical variables. The level of statistical significance was set at p<0.05. Result: No significant differences were observed between groups in terms of age and gender (p>0.05). In individuals with periodontitis, clinically significant indicators reflecting gingival inflammation and periodontal destruction were found to be significantly higher compared to healthy groups (p<0.05). Smokers had lower gingival index and bleeding on probing values compared to non-smokers (p>0.05). Arginase-1 and iNOS levels in gingival tissue samples were elevated in the periodontitis group (p<0.05). Both proteins were effective in distinguishing the periodontitis group from the periodontally healthy group; however, the highest classification success was determined to belong to the iNOS protein (p<0.05). Conclusion: The results of this study indicate that both M1 and M2 macrophage responses are increased in individuals with periodontitis, but smoking use significantly enhances the inflammatory response toward the M1 phenotype. Smoking was found to enhance the proinflammatory process in periodontal tissues by increasing iNOS levels; in contrast, the Arginase-1 response was more pronounced in non-smoking individuals with periodontitis. These findings suggest that smoking is an important environmental factor that alters macrophage polarization in the pathogenesis of periodontitis and shifts the biological balance of the host response toward an M1- dominant inflammatory profile. In future studies in a similar population, the combined evaluation of cell typing and products may facilitate a clearer interpretation of the subject. Keywords: Periodontitis, Macrophage, Polarization, Smoking