The Effect Of IL-6 And IL-8 On The Development Of Reflux Esophagitis, Barrett's Esophagus And Esophageal Adenocarcinoma

Objective: To establish a kind of new and safe animal model of reflux esophagitis (RE),Barrett's esophagus (BE) and esophageal adenocarcinoma (EA )and expore the effect of IL-6 and IL-8 on the development of reflux esophagitis,Barrett's esophagus and esophageal adenocarcinoma .Methods:150 Sprague-Dawley male rats were randomized into 4 groups, including control group(nonreflux group),iron group,reflux group and reflux plus iron group. Esophagoduodenostomy was operated in the last two groups and sham operation in the former two groups. After 2 weeks, Iron Dextran was injected in peritoneal cavities of the rats in iron group and reflux plus iron group (50mg/kg,twice a week for 18 weeks). 5 rats of each group were sacrificed at the 8th week after operation and others at the 20th week, and esophageal samples were taken. Meanwhile serum was collected from caval vein for the measurement of interleukin-6 (IL-6) and interleukin-8 (IL-8) by enzyme-linked immunosorbent assay (ELISA) .All esophagi were assessed for the presence of cancer, Barrett's esophagus, dysplasia and reflux esophagitis by gross and microscopy observation.Results:At the 8th week after operation, mucosal coarse was seen and epithelial hyperplasia was found by microscopy in the iron group. There were serious injuries in esophagus of iron group and reflux plus iron group. At the 20th week, injuries were more serious. Reflux esophagitis was found in every group except the nonreflux group ,and the incidence of RE is much higher in the reflux group and reflux plus iron group,comparing to the iron group(P<0.01),but there was no significant difference between the two groups((P>0.05). In the iron group,there was no samples with BE,dysplasia or EA .In reflux group ,the incidences of BE and dysplasia were 13.2% and 2.6% respectively,while there was no EA samples.In the reflux plus iron group,the incidences of BE, dysplasia and EA were 38.9%,22.2%,11.1%. While there were more samples with BE and dysplasia in the reflux plus iron group ,comparing to the those of nonreflux group and iron group,but there was no significant difference between them(P>0.05). The incidence of BE in the reflux plus iron group was higher than that of the control group (P<0.05),but there was no significant difference in the incidences of dysplasia and EA between the two groups(P>0.05) .The levels of serum IL-6 and IL-8 in the reflux group and reflux plus iron group were higher than those of the rest (P<0.05),and those of the reflux plus iron group were the highest .In the same group ,the levels of IL-6 and IL-8 increased with worsening mucosal injury from RE to EA through BE and dysplasia. While,the levels of serum IL-6 and IL-8 for dysplasia and EA were higher than those of BE and RE(P<0.05).Conclusions:Rat model with Esophagoduodenostomy may cause reflux esophagitis effectively.Overdose iron taken after the esophagoduodenostomy can promote the injury and induce BE ,dysplasia and EA. The levels of IL-6 and IL-8 may play an important role on the development of RE,BE and EA.