Prolonged lifespans in female nzb/nzw mice treated with the experimental immunoregulatory drug frentizole

Abstract

Autoimmune female New Zealand Black/New Zealand White mice were treated with frentizole, an experimental immunosuppressive drug. Three groups of “young,” 8‐week‐old mice received high‐dose frentizole (80–84 mg/kg/day), low‐dose frentizole (8 mg/kg/day), or no drug (controls); these mice were followed until spontaneous death. Three groups of “old,” 24‐week‐old mice with established lupus‐like disease were treated with high or low doses of frentizole. Old control mice received no drug. After 12 weeks of therapy, surviving old mice were killed. Beneficial therapeutic response was achieved when high‐dose treatment was started at an early age; antiDNA values were suppressed, and longevity was prolonged significantly. Frentizole did not arrest the progression of renal disease in old mice. Glomerulonephritis and vasculitis were the most common causes of death in young and old animals. Twenty‐nine percent of young, high‐dose‐treated mice died with neoplasms. Large glomerular deposits of IgG, IgM, and C3 were present in renal tissue from treated and control mice. Peripheral lymphocyte counts and mitogenic responses of spleen cells were not changed by treatment. The efficacy of frentizole in a murine model of lupus supports its usefulness as an immunoregulatory drug.

Evaluation of memory, learning ability, and clinical neurologic function in pathogen‐free mice with systemic lupus erythematosus

“…The drop in trials to criterion from locus-1 to locus-2 learning did not differ between congenic strains, but there were age-related effects for this measure. The young mice of all strains required significantly fewer trials to reach criterion at locus 2 (smallest difference was in MRL/+ For repeat-tested mice, trials to criterion at locus 1 were lower in relearning than in learning for the MRL/+, NZB, NZB/xid, and NZB/WF, mice (smallest difference was MRL/+ mice: F[1,11] = 7.59, P < 0.02) but not for MRL/lpr mice (F [1,12] …”

“…The drop in trials to criterion from locus-1 to locus-2 learning did not differ between congenic strains, but there were age-related effects for this measure. The young mice of all strains required significantly fewer trials to reach criterion at locus 2 (smallest difference was in MRL/+ mice: F[1,21] = 5.37, P < 0.04), as did older MRL/lpr (F [1,14] For repeat-tested mice, trials to criterion at locus 1 were lower in relearning than in learning for the MRL/+, NZB, NZB/xid, and NZB/WF, mice (smallest difference was MRL/+ mice: F[1,11] = 7.59, P < 0.02) but not for MRL/lpr mice (F [1,12] <l). Mean trials to criterion in learning and relearning, respectively, were 3.23 and 3.08 for MRL/lpr, 3.25 and 2.08 for MRL/+, 5.64 and 2.64 for NZB, 5.91 and 3.18 for NZB/xid, and 2.88 and 2.80 for NZB/WFI mice.…”

“…Renal function was assessed by measurement of serum blood urea nitrogen (BUN) using a colorimetric assay (American Monitor, Indianapolis, IN). Serum was tested for anti-DNA antibodies, a marker of SLE activity (4), using a modified Farr assay (12). Serum concentrations of anticardiolipin antibodies were determined by ELISA because these autoantibodies have been associated with CNS manifestations of SLE (13,14).…”

Quantitative and cytoarchitectural studies of the entorhinal region and the hippocampus of New Zealand Black mice

“…This is an additional parallel to human dementia for which Nandy et al (1978) demonstrated such mechanisms. In this context it is interesting to note that Walker et al (1982) were able to influence the autoimmunologic disease, without, however, considering the central nervous system, and to increase the life expectancy of NZB mice by immunosuppressive therapy.…”

Cyclophosphamide and 15(S)-15 methyl PGE1 correct the T/B lymphocyte ratios of NZB/NZW mice

“…These mice die in renal failure with a 50% mortality by 8 to 9 months of age [6]. Several studies have demonstrated the efficacy of immunosuppressive drug therapy in retarding the progressive renal disease in NZB/W mice [7,8]. Longterm treatment of NZB/W mice with cyclophosphamide reduces mortality, decreases circulating levels of IgG, and substantially reduces levels of immunoreactants in the glomeruli as compared with untreated mice [9,10].…”