Although pro-inflammatory cytokines work as biomarkers in periodontal health assessment in general population has been extensively investigated, the relationships between pro-inflammatory cytokines and gingival health statues among orthodontic patients remain unclear. The present cross-sectional study firstly explored the association between the salivary inflammatory mediators and microbiological and clinical features in orthodontic patients. The result shown that there was only a week positive correlation between the salivary IL–1β and BI, and no other relationship between salivary MIF and IL–1β levels and clinical gingival indices was found, which means both cytokines might not suitable for gingival health assessment among orthodontic patients. Positive correlations were found between salivary IL–1β and MIF levels and total salivary bacteria count in the present study, which indicated that salivary MIF and IL–1β levels were mainly in response to bacterial accumulation. This finding confirms that the immunological cytokines play important roles in host inflammatory response to microbial challenges and contributes new knowledge on this research area.
In the present study, the levels of salivary IL–1β and MIF were selected to explore relationships between immunological, microbiological and clinical parameters among orthodontic patients. IL–1β is a key regulator of the host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption[20,21]. It has been reported that salivary levels of IL–1β was positively correlated with BOP in periodontitis patients[22]. MIF is known to be a pro-inflammatory cytokine involved in macrophage and t-cell activation, IgE synthesis, insulin release, carbohydrate metabolism, cell growth and apoptosis, and tumor angiogenesis[22].An experimental gingivitis study reported that the level of MIF positive correlates with plaque index and gingival index[8].These researches indicate that both cytokines are feasible to be used to assess gingival health statues.
However, none of the clinical parameters: PI, MGI, GBI were significantly correlated with salivary MIF level, and there was only a week positive correlation between the salivary IL–1β and GBI in this study. In the multiple regression model, none of the clinical parameters significantly predicted salivary IL–1β levels. These results might due to the effect of orthodontic treatment which could affect cytokines secretion. Previous studies have shown that IL–1β, IL–6, IL–8 and TNF alpha increased in the GCF when applying orthodontic force[9–11]. Therefore, the secretion of pro-inflammatory cytokines in orthodontic patients is more complicate than that of general population, and pro-inflammatory cytokines working as biomarkers ingingival health status assessment among orthodontic patients requires further study.
The demographic parameters (age, sex, saliva flow rate) did not show a significant association with the salivary IL–1β. A negative correlation was found between salivary MIF levels and age, which suggested that salivary MIF level declines with age, which is consistent with a previous study[8]. However, in the multiple regression model, age was not significantly associated with the salivary MIF level (p>0.05). It is plausible that bacteria number is a stronger factor which conceals the effect of age on salivary MIF level with the present sample size.
In this study, positive correlations were found between salivary IL–1β and MIF levels and total salivary bacteria count, and similar correlation coefficients between the total bacteria count (aerobic and anaerobic), streptococci number and lactobacilli number with IL–1β levels which indicates that no specific bacteria combinations might be associated with gingivitis. These results are in general agreement with a previous study, which investigated a larger sample size and reported the detection of multiple pathogenic species in saliva, rather than the presence of any specific pathogens in saliva, which were associated with periodontitis24. Although another study reported that higher GCF levels of IL–1βcorresponded with higher proportions of orange and red complex species in periodontitis patients[23],however, for the subjects in our study who only have gingivitis, specific pathogenic species may not have yet established.
The present study appears to be the first study try to explore the relationship of the salivary pro-inflammatory cytokines levels and gingival health statues, as well as the relationship of the salivary pro-inflammatory cytokines levels and oral bacterial loads among patients undergoing FOAT. Our findings indicate that IL–1β and MIF may be useful and appropriate biomarkers to reflect oral bacterial loads. However, since this study was a cross-sectional study with a limited sample size, it is premature to extrapolate these results to the general population. Moreover, although the analysis of salivary biomarkers offers advantages such as collection of whole saliva is easy and noninvasive, there are also some disadvantages to using whole saliva for diagnostic purposes, such as saliva contains GCF, oral bacteria, cells and other sources that make identification of the exact site of disease activity difficult[5].Nonetheless further study of the correlations between cytokines levels and oral microbe loads in general population is warranted.