Dapsone at onset of diabetes lowers glycated hemoglobin and delays death in NOD mice.

Dapsone (4,4'-diaminodiphenyl sulfone) is a compound that has a large clinical experience due to its antimicrobial effects against mycobacterium leprae, the causative agent of leprosy. It is increasingly used in a number of clinical situations where inflammation may play an ancillary role. An inhibitory effect of the drug or lack thereof in the cumulative incidence or propagation of diabetes mellitus in the NOD mouse has mechanistic as well as therapeutic implications. We previously showed that dapsone administered continuously as a percentage of food to NOD mice inhibits the cumulative incidence of diabetes in a dose dependent fashion. In the present experiment, female NOD litter mates were randomized to receive dapsone (0.001% w/w as a percentage of food) at onset of diabetes. There were no differences in weight, blood glucose, or glycated hemoglobin at 10 weeks of age among the animals that were ultimately to receive dapsone (n = 10), mouse chow alone (n = 9), or those who did not develop diabetes (n = 3). The mean time to onset of diabetes, mean blood glucose at onset, and mean glycated hemoglobin at onset did not differ between animals who did or did not receive dapsone. Animals receiving dapsone had significantly (p < or = 0.03) lower glycated hemoglobin at weeks 2, 3, and 4 following the onset of diabetes and lived significantly longer following diagnosis of diabetes (7 vs. 4 weeks, p < 0.05). In conclusion, dapsone modulates the progression of autoimmune diabetes in the NOD mouse even when administered after the initiation of hyperglycemia.

Dapsone decreases the cumulative incidence of diabetes in non-obese diabetic female mice.

Dapsone (4,4'-diaminodiphenyl sulfone) has a large clinical experience due to its antimicrobial effects against Mycobacterium leprae, the causative agent of leprosy, and is used clinically where inflammation mediated by neutrophils is perceived to play a role. We administered dapsone in two concentrations (0.001% and 0.0001% w/w of diet) to 30 female non-obese diabetic (NOD) mice to explore the effect of dapsone on the development of IDDM following either a 1-week pulse or 20 weeks of continuous oral dapsone administration. Those mice receiving either the high or low doses of dapsone in the continuous group had a significantly reduced cumulative percentage of onset of IDDM. One of the seven mice given 0.0001% dapsone became diabetic (age 25 weeks), while none of the eight high dose (0.001%) mice developed the disease. Histological examination of pancreatic sections revealed islet infiltration in all groups of animals. The pulse and continuous experiments showed no statistically significant difference in the frequency or severity of lymphocytic infiltration. Dapsone administration did not inhibit growth, and growth rates were greater in those animals receiving the higher dapsone dose compared with the lower dose comparable to controls. We studied whether dapsone influenced murine lymphocyte function in addition to the published effects of the drug on neutrophils. At doses approximating those achieved in vivo (0.4 and 2 micrograms/ml), dapsone was found to inhibit murine splenocyte IL-2 and IL-4 secretion in response to concanavalin A. In view of the wide clinical experience with dapsone, randomized trials of the drug in new onset diabetes may be warranted.