PMID: 9640625Jun 26, 1998Paper

Mycophenolate mofetil reduces production of interferon-dependent major histocompatibility complex induction during allograft rejection, probably by limiting clonal expansion

Transplant Immunology
S L LuiP F Halloran

Abstract

The immunosuppressive drug mycophenolate mofetil (MMF) acts by releasing mycophenolic acid (MPA), which inhibits the enzyme inosine monophosphate dehydrogenase (IMPDH) and thus inhibits de novo purine synthesis. Unlike cyclosporine (CsA), MMF has no direct effect on cytokine gene expression in vitro. We examined the effect of MMF, in comparison to CsA, on in vivo production of interferon-gamma (IFN-gamma) in mice. Two stimuli for IFN-gamma induction were used: (1) allogeneic P815 mastocytoma ascites tumour cells and (2) bacterial lipopolysaccharide (LPS). The allogeneic response is dependent on clonal expansion of T cells, while the LPS response is polyclonal and T cell independent. Since major histocompatibility complex (MHC) induction in mouse kidney is IFN-gamma dependent, we assessed the in vivo induction of IFN-gamma indirectly by measuring MHC induction in mouse kidneys in three systems: radiolabelled antibody binding assay, immunoperoxidase staining in tissue sections, and Northern blotting for steady-state MHC mRNA levels. IFN-gamma steady-state mRNA levels were assessed by reverse transcriptase polymerase chain reaction (RT-PCR). In the allogeneic response, MMF (40-160 mg/kg/day) reduced the production of IFN-gamma in ...Continue Reading

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Citations

Jul 6, 2000·Immunopharmacology·T S Mele, P F Halloran
Aug 29, 2003·Molecular and Cellular Biology·Jing Jin GuBeverly S Mitchell
Aug 10, 2000·Clinical and Experimental Immunology·J RincónB Rodríguez-Iturbe
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Oct 4, 2007·Annals of the New York Academy of Sciences·William Thomas Gibson, Michael Reuben Hayden
Dec 4, 2003·Expert Opinion on Pharmacotherapy·Titte R SrinivasHerwig Ulf Meier-Kriesche
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