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 (S...

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Bibliographic Details
Published in:Journal of neuroimmunology 2008-09, Vol.201, p.128-135
Main Authors: Menon, Renuka T.R, Feferman, Tali, Aricha, Revital, Souroujon, Miriam C, Fuchs, Sara
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Antibodies - blood
Body Weight - drug effects
Combined therapy
Cytokines - genetics
Cytokines - metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Therapy, Combination
Experimental autoimmune myasthenia gravis (EAMG)
Female
Gene Expression Regulation - drug effects
Glucocorticoids - therapeutic use
Methylprednisolone - therapeutic use
Muscle, Skeletal - drug effects
Muscle, Skeletal - metabolism
Myasthenia gravis (MG)
Myasthenia Gravis, Autoimmune, Experimental - blood
Myasthenia Gravis, Autoimmune, Experimental - drug therapy
Myasthenia Gravis, Autoimmune, Experimental - pathology
Neurology
Pentoxifylline
Pentoxifylline - therapeutic use
Phosphodiesterase Inhibitors - therapeutic use
Rats
Rats, Inbred Lew
Receptors, Cholinergic - immunology
Severity of Illness Index
Solumedrol
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Summary: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.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2008.05.023