Sara Ellen Walker

Accelerated mortality in young nzb/nzw mice treated with the interferon inducer tilorone hydrochloride.

Abstract Tilorone, 100 mg/kg, was given once a week to two groups of NZB/NZW mice: young mice aged 3 months without overt disease, and 8-month-old mice with established autoimmune disease. Young treated animals died prematurely with severe glomerulonephritis and vasculitis, but lifespans were not shortened in old treated mice. Thymic atrophy was common in treated animals. Tilorone therapy did not affect autoantibody levels; nevertheless, terminal C3 values were decreased significantly in young treated mice. Although interferon activity was detected in sera from young treated mice, it provided no protection from spontaneous autoimmune disease. Tilorone-induced suppression of cell-mediated immunity may have caused accelerated disease and premature death in NZB/NZW mice.

Relation of titred peripheral pattern ANA to anti-DNA and disease activity in systemic lupus erythematosus.

This study compared the clinical usefulness of the peripheral pattern detected in immunofluorescent antinuclear antibody (ANA) testing with anti-DNA measured by the modified Farr technique. 48 patients with active or inactive systemic lupus erythematosus (SLE) were studied at one point in the course of their disease. There was no association between titres of serum giving a peripheral ANA pattern (tp-ANA) and anti-DNA values. Tp-ANA did not correlate with activity of SLE. In contrast with this finding, anti-DNA correlated with severity of renal disease, decreased serum complement, and number of SLE criteria. In a separate group of 9 patients with flare-ups of SLE, tp-ANA and anti-DNA fell as disease activity was controlled. Nevertheless, these two parameters were independent of one another. It was concluded that tp-ANA did not accurately reflect anti-DNA or activity of SLE.

High incidence of neoplasms in female NZB/NZW mice treated with pulse doses of cyclophosphamide

The immunosuppressive properties of cyclophosphamide prevent formation of anti-DNA antibodies and prolong lifespans in autoimmune NZB/NZW mice, an animal model of systemic lupus erythematosus. In the current study, NZB/NZW mice were treated with weekly doses of cyclophosphamide to determine if intermittent pulses of the drug were effective therapy. Life-long treatment with cyclophosphamide, 56 mg/kg/week, was started at the mean age of 6 weeks; results were compared with saline-injected control mice. Pulse therapy with cyclophosphamide suppressed anti-DNA antibody levels, prevented severe glomerulonephritis and prolonged longevity. Seventeen of 19 treated mice developed neoplasms; 7 of these immunosuppressed animals had 2 to 4 separate neoplasms. Examination of earlier studies in this laboratory in which NZB/NZW mice were treated each day with cyclophosphamide showed that daily and weekly therapeutic regimens had similar immunosuppressive and oncogenic effects.

The course of autoimmune disease in parous NZB/NZW mice

Abstract In a study designed to investigate the effects of pregnancy and parturition on spontaneous lupus-like disease in NZB NZW mice, 24 female mice were allowed to breed repeatedly with male NZB NZW mice. Control female mice were caged separately without male mice. Seven months after the study began, the extent of autoimmune disease in parous and control animals was determined by assessing anti-DNA antinuclear antibodies, and the severity of renal lesions. Disease activity in both groups of mice was the same, indicating that pregnancy and parturition had no influence on autoantibody levels or severity of renal disease. It was concluded that bearing young had no effect on the course of autoimmune disease in NZB NZW mice.