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

• Published in: Journal of neuroimmunology Vol. 201; pp. 128 - 135
• Main Authors: Menon, Renuka T.R, Feferman, Tali, Aricha, Revital, Souroujon, Miriam C, Fuchs, Sara
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.09.2008
• 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; Pentoxifylline; Experimental autoimmune myasthenia gravis (EAMG); Solumedrol; Combined therapy; Myasthenia gravis (MG)
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2008.05.023

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.