Successful treatment of autoimmune manifestations in MRLI and MRLn mice using total lymphoid irradiation (TLI)

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Abstract

The autoimmune manifestationsof MRL-++ (MRLn) and MRLMp-lprlpr (MRLl) murine models of systemic lupus erythematosus (SLE) were successfully reversed following total lymphoid irradiation (TLI) therapy consisting of 8–12 daily fractions of 200 rad. Following radiotherapy the characteristic lymphadenopathy of MRLl disappeared, proteinuria was 334 mg% compared to a peak of 2272 mg% in untreated controls, and the median survival time was prolonged to 423 days compared to 214 days in untreated mice. The albuminuria of TLI-treated MRLn mice was 194 mg% compared to 1180 mg% in untreated controls. The survival of treated MRLn mice was prolonged to a median of 389 as compared to 190 days in untreated controls. The effect of TLI on antiDNA antibodies in both MRLl and MRLn was less remarkable. However, the antiDNA activity reached normal levels in most long-living mice. The most impressive finding was complete reversal and/or prevention of the SLE-like glomerulonephritis in MRLl mice as documented by light and electron microscopy. Immunomanipulation with TLI should be further evaluated as a possible treatment modality in intractable human autoimmune disorders.

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