The Expression And Clinial Significance Of TNF-α And IL-4in Chronic Terminal Ileiti

Objective This study was aimed to investigate the expression of tumor necrosisfactor-a（TNF-a） and interleukin-4（IL-4） in experimental terminal ileum, and to evaluateimpacts of TNF-a and IL-4on occurrence，development and treatment of Chronic TerminalIleiti.Methods60healthy male sparague dawley rats were randomly divided into three groups:control group （A）, model group （B）, and suture group （C）. Group A were given Celiacanesthesia,group B were given ileum-caecum side-to-side intestinal anatomists, respectively,while group C were sutured in terminal ileum. These rats were put to death after2and8weeks, respectively, and their terminal ileum was used as specimen and detected theexpression levels of TNF-α mRNA and IL-4mRNA.The remaining specimens were soaked in4%formaldehyde for24hours, and were undergone HE and immunohistochemistry stain.Then we observed the pathological and histological change,the positive expression of TNF-aand IL-4, and inflammation scores of the specimen.Results1. General condition:Rats in group A showed glossy hair, free movement, normal appetite,and granular stool. Group B and group C started to show weakness, weight loss, lazy moveand poor appetite in the3rd postoperative day. After12days all the SD rats began to recover,whilst weight recovery of the rats in group B was slower than the other two groups before2weeks. However, there were no significant difference between the three groups after3-8weeks.2. Gross pathological score of the terminal ileum: After2weeks, there were acuteinflammation reponses in group B and group C, the score of these two groups was notstatistically different （P＞0.05）. After8weeks, rat the terminal ileum became intestinaladhesive and narrow in Group B.And the score of group B was significantly different fromscores of group A and C.（P<0.05）. The terminal ileac tissues experienced no significantinflammatory cell infiltration and structural damage in group A and C （P＞0.05）.3. Endoscopic inflammation score of the terminal ileum: At the2^ndpostoperative week,both group B and C experienced neutrophil infiltration in the terminal ileum.The difference ofscores of group B and C were statistically significant （P<0.05） with a lower score in groupC （P <0.05）. At8thweek,under an electron microscope, we saw a large number ofinflammatory cell infiltration, especially lymphocytes,in the mucosa and submucosain groupB. Score of group B, other than group C,was significantly increased. Inflammatory responsewas most obvious in8thweek group B（P＜0.05）.. There was no significant differencesbetween group C and A（P＞0.05）. The inflammation scores were identically in group B from2to8weeks.4. Level of TNF-a in terminal ileum：The expressed level of TNF-a in the three rats washighest in group B（P＜0.05）, and there were significant difference between group B and C（P＜0.05）.After eight weeks of operation, the expressed level of TNF-a rise in Group B and wassignificant different from that A and C （P<0.05）.There was no significant difference betweengroup A and C （P>0.05）.It suggested that the TNF-a had apparent effect on promotinginflammation in the pathogenesis of Terminal ileitis,and was positive correlated with theinflammatory activity.5.Immunohistochemistry showed that the positive expression of TNF-a in the cytoplasm ornucleus turned brownish yellow,2weeks later, group A, B, C terminal ileum ofTNF-alpha expression rates were10.0%,80.0%,70.0%respectively. After8weeks,the rates were10.0%,90.0%,40.0%.In2and8weeks, compared with the three group hadsignificant difference of positive TNF-a rate. After2weeks, group B and C were higherthan group A, After8weeks, group B was higher than group A and C. At2weeks, theabsorbance of the group B and C were higher than group A, but there have nostatistically differences between the two groups （P>0.05）, there have statisticallydifferences between the two groups and group A （P<0.05）. At8weeks, B group washigher than before in the absorbance, group B compared with group C it is lower,there has statistically differences between group B and group C （P<0.05）, but nostatistically differences between group C and group A （P>0.05）.6. IL-4expression level in the distal ileumThe expression level was higher in group A, compared with group B and C, and thedifferences were statistical significant.（P<0.05）.However, there was no significant difference between group B and C（P＞0.05）. After eight weeks of operation, theexpressed levels of IL-4in these three groups had no notable statistical distinction（P＞0.05）. In immunohistochemistry, the cytoplasm and/or membrane turned brownishyellow was defined as IL-4positive.2weeks later, group A, B, C terminal ileum ofTNF-alpha expression rates were80.0%,30.0%,20.0%respectively. After8weeks,the rates were80.0%,90.0%,70.0%.respectively. In2and8weeks, compared with thethree group had significant difference of positive IL-4rate. In2weeks, group A was highestin positive IL-4rate. In8weeks,group B and group C were higher than2weeks, At8th week,There were no statistically difference between three groups （P＞0.05）. At2th week,the absorbance of A group was higher than the group B and C, Compared with A andB, C has significant difference （P<0.05）. there have statistically differences betweengroup A and the two groups （P>0.05）. At8th week,there were no significant differencebetween the three group （P>0.05）. This experiment indicates how IL-4participated in theprocess of falling ill of CTI.Conclusions1.TNF-a was expressed highest in CTI group and its expression level has a positiverelationship with the severity of inflammatory infiltration.2.IL-4was seldom expressed in the intestinal tissue of CTI group,its expression mightsuppress the acute inflammation of CTI and didn’t change significantly in late stage.3. TNF-alpha and IL-4maybe participate in the progress of CTI, the TNF-αpro-inflammatory effect was better than anti-inflammatory effect of IL-4, TNF-αplayed a important role in promoting the development of CTI.