Suppression of experimental autoimmune myasthenia gravis by combination therapy: Pentoxifylline as a steroid-sparing agent

Renuka T.R. Menon; Tali Feferman; Revital Aricha; Miriam C. Souroujon; Sara Fuchs

doi:10.1016/j.jneuroim.2008.05.023

Suppression of experimental autoimmune myasthenia gravis by combination therapy: Pentoxifylline as a steroid-sparing agent

Renuka T.R. Menon, Tali Feferman, Revital Aricha, Miriam C. Souroujon, Sara Fuchs

Life Sciences discipline

Research output: Contribution to journal › Article › peer-review

Abstract

Myasthenia gravis (MG) is frequently treated by corticosteroids such as methylprednisolone. However, continuous treatment with steroids often results in adverse effects. In the present study we evaluated the therapeutic potential of a combination of suboptimal doses of methylprednisolone (Solumedrol) and Pentoxifylline (PTX), a general phosphodiesterase (PDE) inhibitor, in rat experimental autoimmune MG (EAMG). This combined treatment resulted in a pronounced suppressive effect on EAMG and was by far more effective than each of the drugs administered separately at these low doses. The suppressive effect on EAMG was accompanied by decreased humoral and cellular responses to AChR as well as down-regulated mRNA expression levels of Th1 cytokines and IL-10 in lymph node cells and of PDE-4 and cathepsin-l in the muscle. This study demonstrates the potential of PTX as a steroid-sparing agent in the management of myasthenia gravis.

Original language	English
Pages (from-to)	128-135
Number of pages	8
Journal	Journal of Neuroimmunology
Volume	201-202
Issue number	C
DOIs	https://doi.org/10.1016/j.jneuroim.2008.05.023
State	Published - 15 Sep 2008

Bibliographical note

Funding Information:
This research was supported by grants from The Muscular Dystrophy Association of America (MDA), The Association Francaise Contre les Myopathies (AFM) and The European Commission (EC, No QLG1-CT-2001-10918, QLRT-2001-00225 and LSHN-CT-2006-037833).

Keywords

Combined therapy
Experimental autoimmune myasthenia gravis (EAMG)
Myasthenia gravis (MG)
Pentoxifylline
Solumedrol

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10.1016/j.jneuroim.2008.05.023

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title = "Suppression of experimental autoimmune myasthenia gravis by combination therapy: Pentoxifylline as a steroid-sparing agent",

abstract = "Myasthenia gravis (MG) is frequently treated by corticosteroids such as methylprednisolone. However, continuous treatment with steroids often results in adverse effects. In the present study we evaluated the therapeutic potential of a combination of suboptimal doses of methylprednisolone (Solumedrol) and Pentoxifylline (PTX), a general phosphodiesterase (PDE) inhibitor, in rat experimental autoimmune MG (EAMG). This combined treatment resulted in a pronounced suppressive effect on EAMG and was by far more effective than each of the drugs administered separately at these low doses. The suppressive effect on EAMG was accompanied by decreased humoral and cellular responses to AChR as well as down-regulated mRNA expression levels of Th1 cytokines and IL-10 in lymph node cells and of PDE-4 and cathepsin-l in the muscle. This study demonstrates the potential of PTX as a steroid-sparing agent in the management of myasthenia gravis.",

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author = "Menon, {Renuka T.R.} and Tali Feferman and Revital Aricha and Souroujon, {Miriam C.} and Sara Fuchs",

note = "Funding Information: This research was supported by grants from The Muscular Dystrophy Association of America (MDA), The Association Francaise Contre les Myopathies (AFM) and The European Commission (EC, No QLG1-CT-2001-10918, QLRT-2001-00225 and LSHN-CT-2006-037833).",

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AU - Aricha, Revital

AU - Souroujon, Miriam C.

AU - Fuchs, Sara

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N2 - Myasthenia gravis (MG) is frequently treated by corticosteroids such as methylprednisolone. However, continuous treatment with steroids often results in adverse effects. In the present study we evaluated the therapeutic potential of a combination of suboptimal doses of methylprednisolone (Solumedrol) and Pentoxifylline (PTX), a general phosphodiesterase (PDE) inhibitor, in rat experimental autoimmune MG (EAMG). This combined treatment resulted in a pronounced suppressive effect on EAMG and was by far more effective than each of the drugs administered separately at these low doses. The suppressive effect on EAMG was accompanied by decreased humoral and cellular responses to AChR as well as down-regulated mRNA expression levels of Th1 cytokines and IL-10 in lymph node cells and of PDE-4 and cathepsin-l in the muscle. This study demonstrates the potential of PTX as a steroid-sparing agent in the management of myasthenia gravis.

AB - Myasthenia gravis (MG) is frequently treated by corticosteroids such as methylprednisolone. However, continuous treatment with steroids often results in adverse effects. In the present study we evaluated the therapeutic potential of a combination of suboptimal doses of methylprednisolone (Solumedrol) and Pentoxifylline (PTX), a general phosphodiesterase (PDE) inhibitor, in rat experimental autoimmune MG (EAMG). This combined treatment resulted in a pronounced suppressive effect on EAMG and was by far more effective than each of the drugs administered separately at these low doses. The suppressive effect on EAMG was accompanied by decreased humoral and cellular responses to AChR as well as down-regulated mRNA expression levels of Th1 cytokines and IL-10 in lymph node cells and of PDE-4 and cathepsin-l in the muscle. This study demonstrates the potential of PTX as a steroid-sparing agent in the management of myasthenia gravis.

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Suppression of experimental autoimmune myasthenia gravis by combination therapy: Pentoxifylline as a steroid-sparing agent

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