Suppression of experimental autoimmune myasthenia gravis by combination therapy: pentoxifylline as a steroid-sparing agent.
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.
Menon
Renuka T R
RT
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Feferman
Tali
T
Aricha
Revital
R
Souroujon
Miriam C
MC
Fuchs
Sara
S
D000818:Animals; D000906:Antibodies / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D008775:Methylprednisolone / Q000627:therapeutic use*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010431:Pentoxifylline / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D012720:Severity of Illness Index
D000906:Antibodies; D016207:Cytokines; D005938:Glucocorticoids; D010726:Phosphodiesterase Inhibitors; D011950:Receptors, Cholinergic; D010431:Pentoxifylline; D008775:Methylprednisolone