Propentofylline and iloprost suppress the production of TNF-alpha by macrophages but fail to ameliorate experimental autoimmune encephalomyelitis in Lewis rats

Journal of Autoimmunity
S JungH P Hartung

Abstract

Intracellular cAMP levels can be elevated by activation of cAMP-generating adenylate cyclase (AC) or inhibition of cAMP-cleavage by phosphodiesterases. Elevation of intracellular cAMP levels in immune cells inhibits production of some Th1-cytokines, particularly TNF-alpha, and results mainly in downregulation of the immune response. Experimental autoimmune encephalomyelitis (EAE) of Lewis rats is a disease mediated by type 1 T helper lymphocytes and macrophages and serves as a model of multiple sclerosis. In EAE we therefore tested the immunomodulatory potency of an AC-activating, stable prostacyclin analogue, iloprost, and of a potent and non-selective inhibitor of phosphodiesterases, propentofylline, which also has neuroprotective properties. Preventive treatment of Lewis rats with propentofylline (2 x 10 or 12.5 mg/ kg/d), iloprost (2 x 10 or 12.5 micrograms/kg/d), or both did not significantly ameliorate clinical or histological signs of EAE actively induced by immunization with myelin basic protein (MBP) in complete Freund's adjuvant. Furthermore, adoptive transfer EAE (AT-EAE), passively induced by injection of encephalitogenic MBP-specific Th1 lymphocytes, was not altered in its course by the combined application of ilop...Continue Reading

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Citations

May 4, 2011·Acta Cirúrgica Brasileira·Oguzhan KaratepeMurat Aksoy
Jan 12, 2002·Journal of Child Neurology·B AnlarK Yalaz
Nov 5, 2013·Microscopy Research and Technique·Eduardo Fernandes BondanMaria Martha Bernardi
Sep 30, 2020·The Korean Journal of Pain·Geun Joo ChoiJin Soo Ko
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Roberta GiordoGianfranco Pintus
Oct 27, 2010·Neurochemistry International·D Aguado-LleraE Arilla-Ferreiro

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