Partial characterization of the enhanced survival of female NZB/W mice treated with lithium chloride.

ABSTRACT

Previous investigations have indicated that initiation of LiCl treatment (4 mg/day) of female NZB/W mice at 10 weeks of age led to enhanced survival of 50% of the mice to > 11 months of age (Lithium, 3, 61-67, 1992). The present results indicate that this enhancement of survival is dose dependent in that 2 mg 7LiCl/day was less effective than 4 mg 7LiCl/day. Daily treatment of groups of mice with 2 or 4 mg LiCl per day starting at 8 weeks of age led to the survival of 40% and 70%, respectively, of the mice at 40 weeks of age, a time when only 10% of the untreated mice remained alive. Initiation of treatment with 2 mg 7LiCl/day after the disease process was evident (24 weeks of age) led to diminished effectiveness. Parallel experiments with mice treated with 4 mg 7LiCl/day revealed 60% long-term survivors in the early treatment groups and 33% in the delayed treatment groups. Cessation of treatment in both groups led to some additional deaths, but 20-27% of the mice remained alive at 60 weeks of age, even though animals had detectable levels of anti-ssDNA antibodies in their serum. Additional experiments with 2 and 4 mg 7LiCl/day in NZB/W mice pretreated with C. parvum-PER, a treatment previously shown to enhance survival (Int. J. Immunopharmac., 14, 35-41, 1992), indicated that the effect of the two modalities was not additive. The results presented indicate that treatment of NZB/W mice with LiCl leads to very effective prolongation of survival by unique mechanisms, possibly involving alteration of the effector phase of autoimmune damage to the kidney or the susceptibility of kidney elements to immune-mediated damage leading to renal failure.