A novel antifolate, MX-68, inhibits the development of autoimmune disease in MRL/lpr mice.

Abstract

We compared a novel unpolyglutamable antifolate, MX-68, with polyglutamable antifolate, methotrexate (MTX), for treatment of an autoimmune kidney disease which develops spontaneously in MRL/Mp-lpr/lpr (MRL/lpr) mice. Oral administration of either MX-68 or MTX was commenced in 8-week-old female mice and continued 3 times a week until they reached 30 weeks of age. MX-68 delayed the onset of proteinuria and prolonged life span dose-dependently. Furthermore, it suppressed the elevation of serum blood urea nitrogen and cholesterol levels. MX-68 was as effective as MTX at ameliorating events which accompany the development of lupus nephritis, despite that MX-68 did not undergo polyglutamation. These ameliorative effects of MX-68 and MTX did not occur via inhibition of either autoantibody production or cell proliferation. Neither compound suppressed age-dependent elevation of immune complexes or antibodies for single-stranded DNA and TNP in serum nor did they influence the associated enlargement of lymph nodes and spleen. We conclude that MX-68 is beneficial for the treatment of autoimmune kidney disease in mice and may be useful for other related diseases such as systemic lupus erythematosus.

• Authors: M Mihara, N Takagi, K Urakawa, Y Moriya, Y Takeda
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 113 Issue 4 Pg. 454-9 (Aug 1997) ISSN: 1018-2438 [Print] Switzerland
• PMID: 9250591 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Antigen-Antibody Complex
• Autoantibodies
• DNA, Single-Stranded
• Folic Acid Antagonists
• N-(1-((2,4-diamino-6-pteridinyl)methyl)-3,4-dihydro -2H-1,4-benzothiazine-7-carbonyl)-L-2-aminoadipic acid
• Picrates
• 2-Aminoadipic Acid
• Cholesterol
• picric acid
• Methotrexate

Topics

• 2-Aminoadipic Acid (administration & dosage, analogs & derivatives, chemistry, therapeutic use)
• Administration, Oral
• Animals
• Antigen-Antibody Complex (analysis)
• Autoantibodies (analysis, metabolism)
• Autoimmune Diseases (drug therapy, prevention & control)
• Blood Urea Nitrogen
• Cell Division (drug effects)
• Cholesterol (blood, metabolism)
• DNA, Single-Stranded (immunology)
• Dose-Response Relationship, Drug
• Female
• Folic Acid Antagonists (administration & dosage, therapeutic use)
• Kidney Diseases (drug therapy, immunology, prevention & control)
• Lupus Nephritis (drug therapy, prevention & control)
• Lymph Nodes (pathology)
• Methotrexate (administration & dosage, analogs & derivatives, chemistry, therapeutic use)
• Mice
• Mice, Inbred MRL lpr
• Picrates (immunology)
• Proteinuria (drug therapy, prevention & control)
• Specific Pathogen-Free Organisms
• Spleen (pathology)