LITHIUM-CHLORIDE ENHANCES SURVIVAL OF NZB W LUPUS MICE - INFLUENCE OFMELATONIN AND TIMING OF TREATMENT/

Daily administration of 4 mg (LiCl)-Li-6 to groups (15 mice/group) of female NZB/W mice starting at 8 weeks of age led to long-term survival (44 weeks of age) of 73% of the mice when injections were performed b etween 08:00 and 10:00 h and 67% of mice when injections were performe d between 17:00 and 19:00 h. Untreated controls were dead by 34 weeks of age and the differences between untreated and treated groups was si gnificant (P less than or equal to 10(-4)). In contrast, daily adminis tration of melatonin (100 mu g/mouse) did nor significantly enhance su rvival when injections were performed between 17:00 and 19:00 h but di d enhance survival when given between 08:00 and 10:00 h (P less than o r equal to 10(-3)). Differences between the two melatonin groups was a lso significant (P less than or equal to 0.05). Mice treated with Li p lus melatonin exhibited survival curves identical to mice treated with Li alone. Therefore, the Li effect was dominant and survival was not altered by melatonin. Cessation of treatment in long-term survivors at 44 weeks of age led to the rapid death of 80% of the mice previously treated between 17:00 and 19:00 h (Li, Li + melatonin). In contrast, o nly 40% of the long-term survivors in the other groups had died by 66 weeks of age (22 weeks posttreatment). Thus the p.m. groups were less protected from disease reactivation than were the a.m. groups. Neither Li, melatonin, nor Li+melatonin influenced anti-gp70 or anti-ssDNA le vels in serum, but Li treatment maintained renal function as determine d by proteinuria scores. These findings indicate that the effectivenes s of Li is probably not related to melatonin metabolism and immunomodu lating influences, but the influence of other neuroendocrine Variables cannot be eliminated.