METHOTREXATE TREATMENT IN MURINE EXPERIMENTAL SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) - CLINICAL BENEFITS ASSOCIATED WITH CYTOKINE MANIPULATION

The objective of this study was to determine the effects of Methotrexa te (MTX) on the development and the course of experimental murine SLE, as well as on the cytokine profile involved in the disease. SLE was i nduced in naive BALB/c female mice by injection of the human anti-DNA MoAb bearing a common idiotype (16/6 Id). Six weeks following immuniza tion, when high levels of autoantibodies were demonstrated, the mice w ere treated with MTX (2 mg/kg once a week) for a period of 10 months. MTX treatment had no effect on 16/6 Id-induced autoantibody production . However, MTX treatment had beneficial effects on the clinical manife stations of the experimental disease (i.e. leucocyte counts, levels of protein in the urine and immune complex deposits in the kidneys). Thu s, only 20% of 16/6 Id-immunized BALB/c mice that were treated with MT X had immune complex deposits in their kidneys compared with 100% of S LE-afflicted BALB/c mice that were not treated. We have observed a sig nificant elevation in IL-1, tumour necrosis factor (TNF) and IL-10 sec retion in BALB/c mice afflicted with experimental SLE. IL-2, IL-4, IL- 6 and interferon-gamma (INF-gamma) levels were decreased in these mice compared with the levels detected in healthy controls. Treatment with MTX reversed the levels of all the above cytokines to normal levels o bserved in control mice. These studies demonstrate therapeutic effects of MTX on murine experimental SLE. The normal cytokine profile observ ed following treatment with MTX is suggested to play a role in the ame lioration of the clinical manifestations of experimental SLE.