Abstract
11-Keto-β-Boswellic acid (KBA) has been shown to prevent infiltration of lymphocytes
into pancreatic islets and appearance of peri-insular apoptotic cells in an animal
model of autoimmune diabetes caused by injection of Multiple Low Doses of Streptozotocin
(MLD-STZ), which is a chemical compound belonging to the class of nitrososureas. The
aim of this work was to study whether or not KBA can also prevent/attenuate infiltration
of lymphocytes into pancreatic islets and appearance of peri-insular apoptotic cells
in an animal model of autoimmune diabetes caused by genetic dysfunction resembling
human type 1 diabetes in several important features. Four weeks old female NOD mice
received daily i.p. injections of 7.5 mg/kg of KBA over a period of 3 weeks. Compared
to 4 weeks old animals there was significant infiltration of lymphocytes (CD3) into
pancreatic islets and appearance of peri-insular apoptotic cells in the period between
4 and 7 weeks. During this time plasma glucose dropped significantly and body weight
did not increase. As far as pro-inflammatory cytokines are concerned, except a small
increase of IFN-γ, there was no change in the blood. In mice that had been treated
with KBA between 4 and 7 weeks after birth no significant infiltration of lymphocytes
into pancreatic islets and appearance of peri-insular apoptotic cells was observed,
when compared to 4 weeks old mice. Moreover, there was no drop of blood glucose and
the animals gained body weight. It is concluded that – similar to the model of MLD-STZ-diabetes
– also in the NOD mouse model KBA is able to attenuate or even prevent development
of insulitis, suggesting that KBA protects islets from autoimmune reaction regardless
whether the signal is provided by a chemical compound or by genetic dysfunction. Whether
this also holds for human type 1 diabetes remains to be established.
Key words
boswellic acids - NOD mice - prevention - insulitis - histochemistry - cytokines
