Rolipram suppresses experimental autoimmune neuritis and prevents relapses in Lewis rats.
Rolipram, a phosphodiesterase type 4 inhibitor, can markedly down-regulate antigen-driven T cell proliferation and suppress TNF-alpha production in vitro and in vivo. Here we report the effects of Rolipram on experimental autoimmune neuritis (EAN), which can be induced by immunization with myelin components of the peripheral nervous system (PNS) combined with Freund's complete adjuvant (FCA), and which represents a CD4+ T cell-mediated animal model for human Guillain-Barré syndrome. EAN induced in Lewis rats by inoculation with the PNS P2 protein peptide 57-81 and FCA was strongly suppressed by Rolipram administered twice daily intraperitoneally from day 9 post immunization (p.i.), i.e. after onset of clinical EAN. Suppression of EAN was associated 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 prolongation of treatment resulted in the prevention of clinical EAN relapse. There was no relationship between clinical EAN relapse and high levels of TNF-alpha. 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.
Zou
L P
LP
Department of Clinical Neuroscience, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Deretzi
G
G
Pelidou
S H
SH
Levi
M
M
Wahren
B
B
Quiding
C
C
van der Meide
P
P
Zhu
J
J
D000818:Animals; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D020889:Rolipram / Q000008:administration & dosage / Q000627:therapeutic use*; D055502:Secondary Prevention; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007074:Immunoglobulin G; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D020889:Rolipram