The Immunity Effect Of Interleukin-27 In Clostridium Difficile Induced Colitis

Objective: IL-27 is an important cytokine to regulate host immune response.However,its role in C.difficile-induced intestinal inflammation remains unclear.This study aim to determine the expression of IL-27 during C.difficile infection and to investigate the role of IL-27 in modulating C.difficile-induced inflammation and its mechanism.Methods: The expression of IL-27 during C.difficile infection was determined by ELISA,and the correlation analysis was performed to assess the association of IL-27 expression with laboratory parameters.The pathway of production IL-27 in BMDC induced by C.difficile was studied by Western blot.Wild-type(WT)and IL-27 receptor(IL-27R)/WSX-1knockout(KO)mice were used to establish an experimental model of C.difficile infection and then the level of cytokines were measured by q-PCR and ELISA.After treatment with recombinant IL-27,the cytokines were detected and make an initial research about its mechanism.Further more,chemokine CXCL13 was determined in infected patients and mice and analyzed retrospectively based on laboratory parameters.Results: IL-27 concentration in serum and fecal samples from CDIpatients was significantly higher compared with that from diarrhea patients without CDI and that from healthy controls.C.difficile-induced DCs could produce IL-27 by activating the MAPK ? AKT ? JAK pathway.In experimental C.difficile infection,IL-27 were also markedly increased in serum and infected colon tissues.IL-27 R KO mice exhibited lower survival rates,higher weight loss,decreased bacterial clearance from intestinal tract,and enhanced colon inflammation compared with WT mice,suggesting that IL-27 may protect mice from C.difficile infection.Direct application of recombinant IL-27 could increase survival rates and ameliorate the CDAD symptom after C.difficile infection,which was associated with increased IFN-? in infected colon tissue,indicating a critical role of this cytokine in C.difficile infection.IL-27 priming displayed marked increase of the ability of peritoneal macrophages to phagocytose C.difficile in vitro.Furthermore,CXCL13 was also found upregulated in patients with CDI and CDI mice,suggesting that CXCL13 may be involved in CDI.Conclusion: IL-27 expression was enhanced and may play a protected role during CDI.CXCL13 was also up-regulated in C.difficile infection,and may be pathogenically involved in CDI and served as a potential new biomarker for diagnosis and prognosis in CDI.