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Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.

Abstract
Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn's disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.
AuthorsQing-Kang Lv, Ju-Xiong Liu, Su-Nan Li, Ying-Jie Gao, Yan Lv, Zi-Peng Xu, Bing-Xu Huang, Shi-Yao Xu, Dong-Xue Yang, Ya-Long Zeng, Dian-Feng Liu, Wei Wang
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 16 Issue 11 Pg. 26654-66 (Nov 06 2015) ISSN: 1422-0067 [Electronic] Switzerland
PMID26561804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Immunosuppressive Agents
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Interleukin-12
  • Interferon-gamma
  • Trinitrobenzenesulfonic Acid
  • Mycophenolic Acid
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Cell Differentiation (drug effects, immunology)
  • Colitis (chemically induced, drug therapy, immunology, pathology)
  • Crohn Disease (chemically induced, drug therapy, immunology, pathology)
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Immunosuppressive Agents (pharmacology)
  • Interferon-gamma (genetics, immunology)
  • Interleukin-12 (genetics, immunology)
  • Interleukin-1beta (genetics, immunology)
  • Interleukin-6 (genetics, immunology)
  • Mice
  • Mice, Inbred BALB C
  • Mycophenolic Acid (analogs & derivatives, pharmacology)
  • Spleen (drug effects, immunology, pathology)
  • Th1 Cells (drug effects, immunology, pathology)
  • Th1-Th2 Balance (drug effects)
  • Th2 Cells (drug effects, immunology, pathology)
  • Trinitrobenzenesulfonic Acid
  • Tumor Necrosis Factor-alpha (genetics, immunology)

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