Suppression of experimental autoimmune neuritis by phosphodiesterase inhibitor pentoxifylline.
Phosphodiesterase inhibitor pentoxifylline (POX) has been shown to have multiple immunomodulatory effects in vitro and in vivo. It inhibits T cell proliferation, T helper 1-type cytokines, and tumor necrosis factor. We postulated that POX might have an in vivo immunomodulatory effect on a T-cell-mediated autoimmune peripheral nervous system disease, experimental autoimmune neuritis (EAN). We investigated the effect of POX on EAN in rats immunized with peripheral nerve myelin containing neuritogenic peptide SP26. At 200 mg/kg/day, there was significant suppression of clinical EAN, weight loss, and T cell proliferation to SP26 compared to controls. Proliferation of T cells from immunized rats to SP26 was suppressed by POX in vitro. These studies demonstrate a beneficial role for POX in EAN, with potential applicability to human autoimmune demyelination.
Constantinescu
C S
CS
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.
Hilliard
B
B
Lavi
E
E
Ventura
E
E
Venkatesh
V
V
Rostami
A
A
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D002420:Cauda Equina / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D005260:Female; D009185:Myelin Proteins / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D015588:Observer Variation; D010431:Pentoxifylline / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000276:immunology / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D009185:Myelin Proteins; D010726:Phosphodiesterase Inhibitors; D010431:Pentoxifylline