Protection from experimental autoimmune diabetes in the non‐obese diabetic mouse with soluble interleukin‐1 receptor

We have evaluated the effects of a treatment with soluble interleukin‐1 receptor (sIL‐1R) in the accelerated model of autoimmune diabetes induced by cyclophosphamide (CY) in the non‐obese diabetic (NOD) mouse. Prior to the CY challenge (350 mg/kg body weight), female euglycemic NOD mice were randomly divided into three groups (A–C). Groups B and C were treated daily from 1 day before to 13 days after the CY challenge with sIL‐1R at doses of 0.2 and 2 mg/kg body weight. Group A was treated with PBS. By 2 weeks after CY administration, an acute form of autoimmune diabetes with glycosuria, hyperglycemia and severe insulitis occurred in the majority (13/20, 65%) of the control mice (group A). In contrast, repeated injections with sIL‐1R protected NOD mice from insulin‐dependent diabetes mellitus (IDDM) development in a dose‐dependent fashion; the incidence of IDDM was 53.3% (8/15) in the mice treated with 0.2 mg/kg and only 6.7% (1/15) in those treated with 2 mg/kg. However, none of the doses of the sIL‐1R reduced the extent of insulitis in NOD mice. Importantly, the anti‐diabetogenic property of sIL‐1R may not involve major T cell function impairment; accordingly, in parallel experiments, splenic lymphoid cells from NOD mice not challenged with CY, but treated with 2 mg/kg sIL‐1R for 5 consecutive days showed a normal distribution of mononuclear cell subsets and maintained their capacity to secrete interferon‐γ and IL‐2 and to proliferate in response to polyclonal mitogenic stimulation with concanavalin A.