Mycophenolate mofetil and animal models

Abstract

Mycophenolate mofetil (MMF), is the morpholinoethyl ester of mycophenolic acid (MPA). Though initially developed as an anti-rejection treatment, MMF is beginning to find application in more common immune-mediated diseases. MMF has been shown to be effective against transplant-associated vascular disease, lupus and other inflammatory diseases via multiple mechanisms in several animal models. MMF treatment blocks the proliferation of T cells and B cells, attenuates the production of autoreactive IgG and IgM, diminishes complement deposition, and reduces the production of multiple proinflammatory cytokines including TNF-α, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-6 and IL-12. It also increases production of the anti-inflammatory mediator IL-10. In addition, MMF reduces the infiltration of immune cells into sites of inflammation by interfering with the expression of cell-surface molecules critical for this process, including MHC class II, CD40, CD80, CD86, I-A, and ICAM-1. Additional mechanisms involving mannosylation and N-linked glycosylation of cell-surface molecules are only beginning to be investigated. This article will focus on the contribution of animal models of disease as investigational tools in the development of MMF as an immunomodulatory drug. The use of mice, rats, rabbits, monkeys, baboons and interspecific xenografts will be discussed.