The Effect And Underlying Mechanisms Ofinterleukin-33 On The Mice Model Of Cronn's Disease

Objective Crohn's disease(CD)is a chronic and recurrent gastrointestinal inflammation,which happened among the full-intestinal,seriously affects the patient's quality of life.At present CD lacks of effective treatment methods.The pathogenesis of CD is still not clear,but it is known that immune disorder is involved in the process of CD.and it is recorded that the imbalance of Th17/Treg is the one of the pathogenesis of CD.Interleukin-33(IL-33)is a member of IL-1 superfamily,and its ST2L as its receptor.It is reported that IL-33/ST2L signal path is related to the pathogenesis of CD,but so far the public hasn't reach a consensus.This study is to investigate the treatment efficacy and menchanism of IL-33 on trinitrobenzene sulfonic acid(TNBS)-induced CD mice models.Methods CD mice model was made by the anus enema using TNBS,and the IL-33/ST2L signal path was activated or inhabited by injecting intraperitoneally IL-33 or anti-ST2L monoclonal antibody.The 40 mouse were randomly divided into 4 groups:model group(TNBS +PBS),IL-33 treating group(TNBS +IL-33);IgG treating group(TNBS +IgG),anti-ST2L group(TNBS +anti-ST2L).Crohn's disease(CD)was induced with TNBS in all mice.PBS,IL-33,IgG and anti-ST2L antibody were injected intraperitoneally into CD mice model accounting to group on days 1,3,5.After one week,the disease activity index(DAI),tissue damage index(TAI)were evalusted,the pecertage of CD4+IL-17+Th17 cells and CD4+FOXP3 Treg cells were detected by FCM,and the volume of IL-17 and IL-10 in PBMCs were measured with corresponding ELISA kits.Results The behavior of all mice become abnormal after administrating TNBS,including accidie,mental fatigue,piloerection,anorexia,diarrhea,loose stools,stool OB,and even bloody stools;the symptom of TNBS +IL-33 groups is significant milder than other three groups;the symptom of TNBS +anti-ST2L group is more serious than other three groups.(1)The DAI consequence of TNBS +IL-33 group(1.53±0.50)IS significant lower than TNBS +PBS group(2.77±0.52),TNBS +IgG group(2.73±0.53),and TNBS+anti-ST2L group(3.67±0.42);and TNBS +anti-ST2L group is evidently higher than other groups.(2)The TAI consequence of TNBS +IL-33 groups(1.90±0.53)IS significantly lower than TNBS +PBS group(3.00±0.30),TNBS +IgG group(3.07±0.33),and TNBS+anti-ST2L group(4.00±0.16);and TNBS +anti-ST2L group is evident higher than other groups,the variation trend of TAI is consistent with DAI.(3)The percentage of CD4+IL-17+Th17 cells in the lymphocytes of spleen in TNBS +IL-33 group(0.80+0.11)%is significantly lower than TNBS +PBS group(1.38±0.13)%,TNBS +IgG group(1.34±0.10)%,and TNBS +anti-ST2L group(1.87±0.07)%;whereas the percentage of CD4+IL-17+Th17 cells in TNBS+anti-ST2L group is evidently higher than other groups.(4)The percentage of CD4+FOXP3 Treg cells in the lymphocytes of spleen in TNBS +IL-33 group(4.38±0.13)%is significantly lower than TNBS +PBS group(2.80±0.11)%,TNBS+IgG group(2.96±0.13)%,and TNBS+anti-ST2L group(2.41±0.07)%;whereas the percentage of CD4+FOXP3 Treg cells in TNBS+anti-ST2L group is evidently higher than other groups.(5)The volume of IL-17 in peripheral blood TNBS +IL-33 group(127.45±16.78)pg/mg is significantly lower than TNBS +PBS group(227.96±16.53)pg/mg,TNBS +IgG group(211.50±8.82)pg/mg,and TNBS+anti-ST2L group(270.40±8.17)pg/mg;TNBS +anti-ST2L group is evidently higher than other groups.The variation trend of IL-17 is consistent with the percentage of the CD4+IL-17+Th17 cells in the lymphocytes of spleen;(6)The volume of IL-10 in peripheral blood TNBS +IL-33 group(8.09±0.75)pg/mg is significantly hgherr than TNBS +PBS group(4.73±0.71)pg/mg,TNBS +IgG group(4.50±0.41)pg/mg,and TNBS+anti-ST2L group(3.40±0.27)pg/mg;TNBS+anti-ST2L group is evidently lower than other groups.The variation trend of IL-10 is consistent with the percentage of the CD4+FOXP3 Treg cells in the lymphocytes of spleen;Conclusion1.The results of DAI and TDI suggest that tinterleukin-33 can alleviate the symptom of TNBS-induced CD mice model.2.The variation trend of Th17 and Treg cells percentage and the results of IL-17 and IL-10 suggest that IL-33 alleviates the symptom of TNBS-induced CD mice model though altering the balance of Thl7/Treg.