EFFECT OF TENIDAP, A NOVEL ANTIINFLAMMATORY COMPOUND ON ISLET LYMPHOCYTIC INFILTRATION AND DIABETES INCIDENCE IN THE NON OBESE DIABETIC (NOD) MOUSE

Tenidap(R), a novel compound inhibiting cyclooxygenase and lipoxygenase, also possessing an inhibitory effect on interleukin-1 secretion by in vitro activated macrophages, has been administered to the non obese diabetic (NOD) mouse to evaluate its action on the induction and progression of insulitis and the diabetes incidence. Animals were allocated to three groups (group A : control group; group B : 12 mg/kg/day Tenidap; group C : 36 mg/kg/day Tenidap (R); female animals only were followed up to investigate the effect on diabetes incidence. The administration of Tenidap(R) influenced the natural course of insulitis in male NOD mice; thus, at 60 and 100 days of age the mean percentage of infiltrated islets was significantly reduced compared to control animals (p < 0.02). Moreover the severity of lymphocytic infiltration at 60 days of age was reduced in male mice of group B and C compared to control mice (p < 0.004 and p < 0.0001, respectively) whereas at 100 days of age this difference was not significant. However the progression towards severe insulitis in male animals receiving Tenidap (R) was halted compared to control animals. Tenidap (R) had also a significant dose dependent effect at 60 days on the severity of lymphocytic infiltration (group B vs. group C, p < 0.01). By contrast, this agent had no effect on the degree of insulitis and diabetes incidence in female NOD mice. In both sexes at the end of follow-up a significant reduction in body weight was observed in animals of Group C compared to control animals (p < 0.0)2). We conclude that Tenidap(R), at pharmacological doses, reduces the lymphocytic infiltratin in the pancreas of male NOD mice but does not protect female mice from developing the disease suggesting the importance of the sex hormone pattern in the pathogenesis of diabetes in this animal model.