The suppressive effect of cyclophosphamide on low-dose streptozotocin-induced diabetes in mice

We found that low-dose streptozotocin (SZ)-induced diabetes in mice is suppressed by cyclophosphamide (CY) and studied the mechanisms of this suppression. Male CD-1 mice were injected intraperitoneally with SZ (40 mg/kg) for five consecutive days (group SZ). In addition, CY (200 mg/kg) was injected on the first day (group CY-1) or on days 1 and 5 (group CY-2). In group SZ, all mice developed diabetes within nine days after the first injection of SZ. Group CY-1 did not develop hyperglycemia for 14 days and group CY-2 did not develop it throughout the experimental period (40 days). Insulitis was suppressed slightly in group CY-1 and completely in group CY-2. The number of spleen cells did not change in group SZ compared with that before cyclophosphamide treatment. They decreased significantly on days 3 and 7 in both groups CY-1 and CY-2 (p less than 0.01 or p less than 0.05), but then increased significantly on days 14 and/or 21 (p less than 0.01 or p less than 0.05) compared with those before cyclophosphamide treatment. The Thy 1.2- and L3T4-positive cells increased significantly in group SZ but they decreased on days 3 and 7 in both groups CY-1 and CY-2 (p less than 0.01) compared with the controls. These results suggest that (1) this large reduction of lymphocytes at the beginning of SZ treatment may lead to the prevention of hyperglycemia and insulitis, and (2) T-cells, especially L3T4-positive cells may play an important role in the pathogenesis of this type of diabetes.