The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis.
In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) the cytokines tumour necrosis factor-alpha (TNF), lymphotoxin-alpha (LT), and interferon-gamma (IFN-gamma) are of central pathogenetic importance. A therapy capable of stopping neurological deterioration in MS patients is not yet available. Here, we report that rolipram, a selective type IV phosphodiesterase inhibitor, stereospecifically suppresses the production of TNF/LT and less strongly also IFN-gamma in human and rat auto-reactive T cells. Moreover, we show that rolipram is an effective treatment for EAE. Rolipram has extensively been studied in humans for the treatment of depression, but has not yet been marketed. The data presented here identify rolipram as potential therapy for multiple sclerosis and provoke the immediate initiation of clinical trials.
Sommer
N
N
Department of Neurology, Tübingen University, Germany.
Löschmann
P A
PA
Northoff
G H
GH
Weller
M
M
Steinbrecher
A
A
Steinbach
J P
JP
Lichtenfels
R
R
Meyermann
R
R
Riethmüller
A
A
Fontana
A
A
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D009103:Multiple Sclerosis / Q000188:drug therapy; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D020889:Rolipram; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000928:Antidepressive Agents; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020889:Rolipram