Rolipram suppresses experimental autoimmune neuritis and prevents relapsesin Lewis rats

Rolipram, a phosphodiesterase type 4 inhibitor, can markedly down-regulate antigen-driven T cell proliferation and suppress TNF-alpha production in vi tro and in vivo. Here we report the effects of Ralipram experimental autoim mune neuritis (EAN), which can be induced by immunization with myelin compo nents of the peripheral nervous system (PNS) combined with Freund's complet e adjuvant (FCA), and which represents a CD4(+) T cell-mediated animal mode l for human Guillain-Barre syndrome. EAN induced in Lewis rats by inoculati on with the PNS P2 protein peptide 57-81 and FCA was strongly suppressed by Rolipram administered twice daily intraperitoneally from day 9 post immuni zation (p.i.), i.e. after onset of clinical EAN. Suppression of EAN was ass ociated with down-regulated myelin antigen-induced T cell responses as well as down-regulated IFN-gamma and TNF-alpha production A relapse of clinical EAN occurred upon treatment of a short duration (7 days), while prolongati on of treatment resulted in the prevention of clinical EAN relapse. There w as no relationship between clinical EAN relapse and high levels of TNF-alph a. The immunomodulatory effects of Rolipram call for further research into the potential role of drugs acting on the immune system in the treatment of autoimmune diseases. (C) 2000 Elsevier Science Ltd. All rights reserved.