Dopamine receptor antagonism increases autoimmune diabetes severity in NOD mice

DEL BALZO, D; MOTRICH, RD; PENNACCHIO, GE; SOAJE, M; VALDEZ, SR; RIVERO, VE; JAHN, GA; MACKERN-OBERTI, JP

Buenos Aires

Congreso; LXIII Reunión Anual de SAI, I Meeting LASID-SAI-FAIC, IV Meeting LASID, y II Meeting FAIC.; 2015

Sociedad Argentina de Inmunologia

Background: Several studies indicate that dopamine plays a role in the interaction between the nervous and immune systems. Dopamine, by an inhibitory tone, regulates prolactin secretion by lactotroph cells in the hypophysis which in turn could modulate immune cells. Furthermore, it has been reported that some patients with autoimmune diseases course with hyperprolactinemia. Herein, we investigated whether dopamine receptor (DR) antagonism modulate experimental autoimmune diabetes. Methods: NOD mice were subjected to a DR antagonist chronic treatment by daily intraperitoneal injections of eticlopride (Eti, n=9) or saline (untreated, UT, n=8) from 3 to 7 months old. Disease severity was evaluated by the assessment of survival, glucosuria, spleen cells expansion and pancreas leukocyte infiltration. Results: Interestingly, chronic DR antagonist treatment decreased survival rate compared to untreated (UT) mice (UT 87,5% (7/8) vs. Eti 55% (5/9)). Eti administration increased incidence of glucosuria (UT 25% (2/8) vs. Eti 66,6% (6/9)). Furthermore, FACS analyses showed that Eti mice had a 2,6 fold increase in pancreas leukocyte infiltration compared with UT mice. Spleen weight from Eti mice was greater than UT mice (UT 125±10 vs. Eti 177±16 mg; p=0,0184). Although total CD3+CD4+ spleen cells were increased in Eti mice (UT 39,7±3,0 vs. Eti 48,0±1,0%; p=0,0393), no changes were observed in CD8+ or activated CD69+ T cell populations. Conclusions: Although further research is needed, our data support the notion that dopamine and DR axis play a crucial role in autoimmune diabetes progression, suggesting this axis as a potential immunotherapeutic target.