Effect of several kinds of drugs on the development of autoimmunity in MRL/Mp-lpr/lpr mice; lack of correlation between the suppression of autoantibody production and prevention of autoimmune disease.
MRL/Mp-lpr/lpr (MRL/l) mice spontaneously develop autoimmune kidney disease which resembles human systemic lupus erythematosus (SLE). Employing this strain of mouse, we examined the effect of several immunosuppressants and a newly synthetized anti-nephritic agent, 4-chloro-3',6'-dimethyl-2,2'-iminodibenzoic acid (TO-115) on both the development of immunological abnormalities and the clinical symptoms of autoimmune kidney disease. This study aimed to determine how much the magnitude of autoantibody suppression related to the degree of prevention of autoimmune nephritis. Immunological abnormalities were assessed by measuring the serum levels of anti-deoxyribonucleic acid and anti-trinitrophenyl antibodies, rheumatoid factor (RF), and immune complex (IC). The status of autoimmune kidney disease was monitored by means of the appearance of proteinuria and survival time and the measurement of serum levels of blood urea nitrogen (BUN) and cholesterol. Immunosuppressants such as cyclophosphamide (CY), 6-mercaptopurine (6 MP) and sodium aurothiomalate (SAT) remarkably suppressed the development of immunological abnormalities in a dose dependent manner. Interestingly, however, only CY showed the suppressive effect on the development of autoimmune kidney disease with prolongation of survival time and the excretion of proteinuria. In contrast, 6-MP and SAT did not inhibit the development of autoimmune kidney disease. On the other hand, TO-115 did not suppress the development of immunological abnormalities, but it restrained the symptoms of autoimmune kidney disease. Taken together, the suppression of autoantibody production does not always lead to prevention of the development of autoimmune kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Mihara
M
M
Section of Immunopharmacology, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
Ohsugi
Y
Y
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000517:prevention & control*; D001806:Blood Urea Nitrogen; D002784:Cholesterol / Q000097:blood; D003520:Cyclophosphamide / Q000494:pharmacology; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D007105:Immune Complex Diseases / Q000517:prevention & control; D007674:Kidney Diseases / Q000517:prevention & control; D015122:Mercaptopurine / Q000494:pharmacology; D051379:Mice; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D001323:Autoantibodies; D062367:ortho-Aminobenzoates; D006052:Gold Sodium Thiomalate; C057292:4-chloro-3',6'-dimethyl-2,2'-iminodibenzoate; D003520:Cyclophosphamide; D002784:Cholesterol; D015122:Mercaptopurine