| Objective: This cross-sectional study aims to analyze the association between low-to-moderate fluoride exposure and serum inflammation levels,and further explore the mediating effects of inflammatory markers between fluoride exposure and dental fluorosis(DF)risk.Methods: 593 school children aged 7-13 who resided in fluorosis and non-fluorosis area in Tianjin City were recruited as subjects using stratified multistage random sampling method according to regions.The general sociological data of the subjects and their parents were collected through questionnaires and the status of DF in children was detected by professional doctors.The fasting morning urine and venous blood of children were collected.Fluoride ion selective electrode method was used to measure the fluoride concentrations of drinking water and urine;The concentrations of inflammatory markers interleukin-1β(IL-1β)and C-reactive protein(CRP)in serum were determined by enzyme-linked immunosorbent assay.Multivariate linear regression models and log-binomial regression models were established to analyze the associations among fluoride exposure,inflammation levels and DF risks.In addition,the mediating effects of inflammatory markers between fluoride exposure and DF risks were investigated in the mediation models.Results: The fluoride concentrations of drinking water and urinary samples ranged from 0.20 mg/L to 3.90 mg/L and 0.01 mg/L to 5.54 mg/L,respectively.The median and interquartile ranges of drinking water and urinary samples were 1.20(0.70-2.20)mg/L and 0.56(0.16-2.29)mg/L,respectively.Serum inflammatory markers IL-1β and CRP levels ranged from 28.45 pg/ml to 87.92 pg/ml and 5.27 mg/L to 13.16 mg/L,respectively.The median and interquartile ranges of IL-1β and CRP were 58.29(47.15-67.27)pg/ml and 9.17(7.95-10.52)mg/L,respectively.All subjects were divided into high fluoride exposure group and low fluoride exposure group according to the conventional fluoride limit(ie 1.0 mg/L)in China’s domestic drinking water hygiene standards(GB5749-2006).There was significant difference in DF prevalence between high fluoride exposure group and low fluoride exposure group(P < 0.001).A total of 216(74.5%)children in the low fluoride exposure group had normal teeth,and there were no children diagnosed as Moderate DF and Severe DF;210(69.3%)children in the high fluoride exposure group were diagnosed as Mild DF,and 29(9.6%)children were diagnosed as Moderate DF,and there were no children diagnosed as severe DF.Multiple linear regression analysis showed that every 1 mg/L increase in water fluoride content was associated with a 4.73 pg/ml increase in IL-1β(β = 4.73,95% CI: 3.75,5.70)and a 0.58 mg/L increase in CRP(β = 0.58,95% CI: 0.46,0.71);Each 1 mg/L increase in urine fluoride content was related to a 4.57 pg/ml increase in IL-1β(β = 4.57,95% CI: 3.78,5.36)and 0.50 mg/L in CRP(β = 0.50,95% CI: 0.39,0.60).The increase of fluoride concentrations in water and urine had a dose-effect relationship with the concentrations of serum IL-1β and CRP(both P values for trend < 0.001).Log-binomial regression analysis showed that fluoride concentrations was positively correlated with DF risks.(all P values < 0.001).For every 1 pg/ml increase in IL-1β,the risk of DF in the subjects increased by 2.3%(PR: 1.023,95% CI: 1.017,1.028).Among them,the risks of Very mild DF,Mild DF,Moderate DF were increased by 2.5%(PR: 1.025,95% CI: 1.010,1.040),3.3%(PR: 1.033,95% CI: 1.025,1.040)and 8.2%(PR: 1.082,95% CI: 1.045,1.121),respectively.For every 1 mg/L increase in serum CRP,the risk of DF in the subjects increased by 16.8%(PR: 1.168,95% CI: 1.123,1.216).Among them,the risk of Very mild DF,Mild DF,Moderate DF were increased by 25.3%(PR: 1.253,95% CI: 1.122,1.399),25.9%(PR: 1.259,95% CI: 1.191,1.332)and 67.8%(PR: 1.678,95% CI: 1.274,2.211).In addition,serum IL-1β explained 10.1%(95% CI: 6.3%,15.7%),4.4%(95% CI: 0.3%,40.4%)and 10.0%(95% CI: 6.1%,15.8%)of the relationships between water fluoride concentrations and the risks of Overall DF,Very mild DF as well as Mild DF,respectively;IL-1β levels explained 7.6%(95% CI: 3.7%,14.8%),1.5%(95% CI: 0.0%,98.7%)and 8.7%(95% CI: 4.8%,15.2%)of the relationships between urinary fluoride concentrations and the risks of Overall DF,Very mild DF as well as Mild DF,respectively.Similarly,serum CRP explained 8.2%(95% CI: 4.9%,13.4%),5.5%(95% CI: 1.3%,20.8%)and 9.2%(95% CI: 5.5%,14.9%)of the relationships between water fluoride concentrations and the risks of Overall DF,Very mild DF as well as Mild DF,respectively;CRP levels explained 5.8%(95% CI: 3.0%,11.0%),5.8%(95% CI: 1.2%,23.4%)and 6.1%(95% CI: 3.3%,11.0%)of the relationships between urinary fluoride concentrations and the risks of Overall DF,Very mild DF as well as Mild DF,respectively.Conclusions: Low-to-moderate fluoride exposure is positively associated with serum inflammation levels and DF risks among school-age children;serum inflammatory markers IL-1β and CRP are positively associated with DF risks.In addition,IL-1β and CRP may partially mediate the relationship between fluoride exposure and DF risks. |
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