Therapeutic Effect Of Imiquimod On Experimental Colitis In Mice

Background:Imiquimod is a Toll-like receptor agonist that regulates immu-nity and can be used as an immune adjuvant.Ulcerative colitis has a close correlation with immune disorder.Aim:To investigate the therapeutic effect of imiquimod on dextran sulfate sodium(DSS)-induced colitis and explore the underlying mechanisms.Methods:C57BL/6J mice received 3%DSS for 7 days to induce ulcerative colitis.Groups of mice were intraperitoneally injected with dexamethasone(DXM,1.5 mg/kg)or imiquimod(IMQ,30 mg/kg)at the same time daily.During the experimental period,the mortality of each group was recorded,and clinical signs,body weight,stool consistency and visible fecal blood were monitored and recorded daily;colitis was evaluated by disease activity index(DAI)score and by histological score.At the conclusion of the experiment,the level of colonic myeloperoxidase(MPO)activity and the gene expression of tumor necrosis factor-α(TNF-α),interleukin 10(IL-10)and interleukin 6(IL-6)of inflamed colon of each group were assessed by Real-time PCR.Moreover,the serum levels of the cytokines TNF-α,IL-6 and IL-10 were measured by ELISA.Results:Administration of 3%DSS for 7 days successfully induced acute colitis associated with diarrhea,bloody mucopurulent stool,body weight decreases,and other changes,and also the mice have different degrees of death..Colitis severity was significantly ameliorated in the IMQ treatment groups,as determined by hemat-oxylin-eosin(HE)staining and histopathological scores.Moreover,IMQ could slow down weight loss and shorten of the colon.Compared with DSS group,and significantly reduced the activity of MPO(P<0.01)decreased expression of TNF-α,IL-6(P<0.01)and increased expression of IL-10(P<0.05)in colonic tissue The serum TNF-α,IL-6 levels were greatly decreased and IL-10 was increased in IMQ group compared with DSS group(P<0.01),the spleen weight increased(P<0.05).The date difference between the curative effect of IMQ and DXM is not statistically significant(P>0.05).Conclusion:IMQ had beneficial effects on DSS-induced experimental colitis in mice,supporting its further development and clinical application in ulcerative colitis.It was completed probably by inducing of specific immune response,enhancing the body’s immune response.