Oligodeoxynucleotide IMT504: lack of effect on immune parameters during islet regeneration in single dose...

We have shown that oligodeoxynucleotide IMT504 improved blood glucose and islet beta-cell content in streptozotocin (STZ)-induced diabetic rats, inducing early expression of progenitor markers. Here we determined the effect of IMT504 on islet infiltration and on immunomodulatory proteins indoleamine 2,3-dioxygenase (IDO) and TNF-α-stimulated gene/protein 6 (TSG-6) in islets of STZ-diabetic rats, at the time of progenitor markers expression.

Male rats were i.p. injected with STZ [60 mg/kg body weight (BW)] or citrate buffer (control) (day 1). Starting on day 4, STZ animals were daily treated with saline (STZ-saline) or IMT504 (20 mg/kg BW/day s.c., STZ-IMT504) and killed after two consecutive decreases in blood glucose. Islet area and insulin expression, CD3 (T lymphocytes), CD68 (macrophages), IDO and TSG-6 immunostainings were determined. Islet infiltration was also evaluated by haematoxylin staining.

STZ-induced diabetes in rats, with an important decrease in islet area was reversed by IMT504. Diabetes development did not involve islet infiltration, determined by haematoxylin and by the absence of significant T lymphocyte and macrophage presence. IMT504 did not induce changes in these parameters. IDO was not expressed in controls; the percentages of IDO-positive islets were very low and similar in STZ-saline and STZ-IMT504. Scarce TSG-6 was expressed in all groups, without significant differences.

IMT504 improved insulin content but did not alter IDO or TSG-6 staining in islets of STZ-diabetic rats, suggesting that they do not participate in the IMT504-induced repair process. IMT504 did not per se modify leukocyte presence in islets of diabetic rats.