ABSTRACT
1. A strategy is described for evaluating drugs against different phases in the development of an auto allergic disease, experimental allergic encephalomyelitis. It is based on a cell transfer technique whereby the disease is passively transferred with lymphoid cells from actively immunized donor rats to normal syngeneic rats = passive recipients. Drugs may be applied in vivo to either the cell donors or the cell recipients or to cells in vitro whilst in transit; their efficiency being determined by the severity of the passive disease (weight loss, paralysis) in the recipients. 2. Examples are given illustrating the application of these techniques to: (a) evaluating the lymphocyte-deactivating activity of various nitrogen mustards in vitro; (b) recognizing drugs, e.g. gold derivatives, clofazimine, etc. that are not conventional immunosuppressant (or cytostatic) agents which, when given to the recipient animals, may prevent the expression of the adopted disease; (c) comparing some known immunosuppressants for potency, duration of action, etc.; (d) demonstrating the versatility of cycloleucine, ICI-47,776, etc. 3. Some merits of the strategy are discussed vis a vis using the local graft-versus-host reaction in rats to search for new drugs.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Immunosuppressive Agents/pharmacology , Lymphocytes/immunology , Animals , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/immunology , Female , Lymphocyte Transfusion/methods , Male , Rats , Rats, Inbred F344 , Rats, Inbred LewSubject(s)
Autoimmune Diseases , Myositis/immunology , Animals , Aspartate Aminotransferases/blood , Body Weight , Creatine Kinase/blood , Female , Freund's Adjuvant/administration & dosage , Fructose-Bisphosphate Aldolase/blood , Injections, Intralymphatic , Lymph Nodes/immunology , Lymphocytes/immunology , Male , Mitochondria, Muscle/immunology , Muscles/immunology , Muscles/pathology , Mycobacterium/immunology , Myositis/enzymology , Myositis/etiology , Myositis/pathology , Rats , Sarcoplasmic Reticulum/immunology , Subcellular Fractions/immunologyABSTRACT
1. Fenclozic acid (2-(4-chlorophenyl)thiazol-4-ylacetic acid; I.C.I. 54,450; "Myalex") is one representative of a new class of compounds with antiinflammatory, analgesic and antipyretic properties as evidenced by its activity in a variety of tests in rats, mice and guinea-pigs.2. In tests of short duration the potency of fenclozic acid is similar to that of phenylbutazone.3. In tests of longer duration fenclozic acid is more potent than phenylbutazone.4. The activity of fenclozic acid is not mediated by stimulation of the adrenals and the compound is devoid of corticosteroid-like activity.