Mycophenolate mofetil ameliorates perivascular T lymphocyte inflammation and reduces the double-negative T cell population in SLE-prone MRL/pr/lpr mice

Effects on T lymphocyte mediated pathology, phenotypes, and functions in MR Llpr/lpr mice given mycophenolate mofetil (MMF) (100 mg/kg/day) via drinkin g water or controls given ip cyclophosphamide (CYC) injections (1.8 mg/mous e/week) or water were described. Both MMF and CYC treatment diminished kidn ey and large salivary gland perivascular cell infiltrates, reduced profound ly double-negative (DN) T cell frequencies, decreased total lymphocyte numb er in spleen, and increased in vitro proliferative response to Con A. IFN-g amma and IL-10 in supernatants from Con A stimulated spleen cells were augm ented after MMF but not CYC treatment. MMF treatment increased whereas CYC reduced IL-12 in serum. Kidney expressions of IFN-gamma, IL-10, and IL-12 m RNA were unaffected by MMF but decreased by CYC. Our results demonstrate th at MMF and CYC suppress perivascular T lymphocyte inflammation by reducing the DN T cell population and by amelioration of T cell function. The varyin g cytokine patterns suggest different mechanisms of the two drugs. (C) 1999 Academic Press.