Current Studies on the Effect of Antimetabolites in Nephrosis, Other Non-Neoplastic Diseases, and Experimental Animals

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Abstract
Reports in the literature of the suppression by purine antimetabolites of immune responses in animals and of the production of remissions in human non-neoplastic diseases by these agents are reviewed. The toxicity and clinical effect of one such agent, 6-thioguanine (6-TG), in patients with nephrosis, chronic hepatitis, and lupus erythematosus are reported. All of 4 patients with steroid-responsive nephrosis have had complete remissions as a result of administration of 6-TG alone or of 6-TG plus a previously inadequate dosage of prednisone. No definite remissions occurred in 4 steroid-resistant nephrotic patients. Preliminary results of administration of 6-TG to patients with chronic hepatitis and lupus erythematosus are described. A fall in concentration of serum immuno-globulins followed the administration of 6-TG to patients with nephrosis. Administration of this drug produced less suppression of delayed cutaneous reactivity to bacterial or mycotic antigens than did the administration of prednisone. The effect of administration of methotrexate in experimental allergic encephalo-myelitis in guinea pigs as well as the possible mechanisms of action of the antimetabolites are discussed.