The effect of thalidomide on experimental autoimmune myasthenia gravis.
Thalidomide is reported to have immunosuppressive and anti-inflammatory effects which have led to its use in the treatment of a number of immune-mediated disorders including leprosy, prurigo, discoid lupus, and Behcet's disease. In addition, thalidomide has recently been used to prevent immunological rejection phenomena following skin and bone-marrow grafts. The immune responses in these conditions are thought to be cell-mediated. However, little is known about the effectiveness of thalidomide in suppressing antibody-mediated immune responses. In the present study, we have examined the effect of thalidomide in a model antibody-mediated autoimmune disorder--experimental autoimmune myasthenia gravis (EAMG). To induce EAMG, Lewis rats were immunized with acetylcholine receptor (AChR) purified from the electric organ of Torpedo californicus. Groups of rats were treated daily, either with thalidomide in excess of doses reported to prevent graft-versus-host (GVH) disease in bone-marrow-transplanted rats, or with control treatments. Our results show that thalidomide failed to inhibit AChR antibody production despite good absorption and high blood levels of the drug. This suggests that thalidomide is not likely to be generally useful in the treatment of antibody-mediated autoimmune conditions. However the selective effect of thalidomide in suppressing certain presumably cellular immune responses, while sparing antibody production, is inherently interesting, and merits further study.
Crain
E
E
Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205.
McIntosh
K R
KR
Gordon
G
G
Pestronk
A
A
Drachman
D B
DB
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*
D001323:Autoantibodies; D007166:Immunosuppressive Agents; D011950:Receptors, Cholinergic; D013792:Thalidomide