The Prostaglandin E(1) (PGE(1)) Analog Misoprostol Ameliorates Autoimmune Disease and Depletes T Lymphocytes in MRL-lpr/lpr Mice.
MRL-lpr/lpr mice spontaneously develop an autoimmune disease similar to human systemic lupus erythematosus (SLE). Disease manifestations include anti-DNA autoantibody production, arthritis, vasculitis, and an immune-complex glomerulonephritis. The development of autoimmune disease is associated with massive, generalized lymphadenopathy caused by accumulation of an abnormal T-cell population in peripheral lymphoid organs. In MRL-lpr/lpr mice, treatment with E-series prostaglandins ameliorates renal disease and reduces peripheral lymphadenopathy. Little is known about mechanisms of action of E-series prostaglandins in murine lupus or the effects of these agents on other clinically important manifestations of SLE, such as arthritis and vasculitis. To further investigate the effects of an E-series prostaglandin in murine SLE, we administered the prostaglandin, E(1) (PGE(1)) analog misoprostol (1 mg kg(minus sign1) day(minus sign1)) to MRL-lpr/lpr mice for 8 weeks by twice daily subcutaneous injection. At 20 weeks of age, treatment with misoprostol reduced the severity of renal disease and arthritis but did not affect the extent or severity of vasculitis. The beneficial effects of misoprostol on arthritis and renal disease were associated with a significant decrease in splenic and lymph node weight in mice given the PGE(1) analog. This decrease in lymphoproliferation resulted primarily from a generalized reduction in the number of T cells in peripheral lymphoid organs. Thus, T-cell depletion was associated with beneficial effects on arthritis and nephritis in MRL-lpr/lpr mice, supporting a role for T lymphocytes in these disease processes. The ability of E-series prostaglandins to favorably modify autoimmune disease in this murine model suggests that misoprostol may be a useful adjunct to current therapies for the treatment of patients with SLE.
Best, V; Ruiz, P; Spurney, RF
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