Expression And Clinical Significance Of IL-4 And IL-6 In Different Subtypes Of Gastroesophageal Reflux Disease

Objective: To investigate the expression of IL-4,IL-6 in Barrett esophagus(BE),Erosive esophagitis(EE)and Nonerosive reflux disease(NERD)and the role they played in Gastroesophageal reflux disease(GERD).Methods: Patients of BE,EE,NERD and control group were carefully selected according to the results of GERD Questionnaire and endoscopy.High resolution manometry(HRM)and 24-hour ambulatory esophageal pH monitoring were used to estimate the GERD patients' esophageal motility and acid exposure respectively.Esophageal biopsies taken at endoscopy in all four groups were observed in microscopy for histopathology,and tested by immunohistochemistry(IHC)staining for cytokines IL-4 and IL-6,which were also detected in patients serum by enzyme-linked immune sorbent assay(ELISA).Results: In the 24 h pH monitoring,DeMeester score showed no significant differences in three GERD subtype groups(P> 0.05),neither were the results of 4<pH<7(weak acid)reflux event nor the total reflux event.The event of pH<4(acid)reflux was significantly lower in NERD group(P<0.05).The HRM results showed no significant difference between the three groups of GERD patients in LES length,LES static pressure and residual pressure,and DCI score(P> 0.05).In the comparison of the four groups including the control of the esophageal mucosal histopathological grading,BE and EE had significantly higher inflammatory score(P<0.05);and the difference between NERD group and the control was not significant.Detecting the IL-4 expression in specimens of esophageal,we found the level increased the inflammatory condition of GERD worsened.But there was no considerable difference between the four groups(P>0.05).The serum IL-4 level in BE and EE were significantly higher than those in the other two groups(P<0.05).The expression of IL-6 in the esophagus of NERD group and the control was considerably low or not even none.Worsening of inflammation condition increased the expression level of IL-6 and the IL-6 level in the EE group was markedly higher than that in the control group(P<0.05).The serum IL-6 level of BE group and EE group was significantly higher than those in the other two groups(P<0.05),but it was significantly lower in BE group than in the EE group(P<0.05).And there was no significant difference of serum IL-6 between NERD group and the control.Conclusions: Acid exposure is not the dominant factor in the GERD development process.The endoscopic aggravation of the esophagus in the process of GERD has no significant effect on esophageal dynamics.Histological inflammation level of GERD esophageal mucosal epithelium is increased with the deterioration of esophagitis.Though there was some inflammatory change in esophageal pathology of NERD,it was not meaningful comparing with normal esophagus.IL-4 and IL-6 have higher serum concentrations in esophagitis and Barrett esophagus patients,but IL-6 is more significantly expressed in esophagus between different subtypes of GERD.