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

Eur J Immunol. 1994 Aug;24(8):1843-7. doi: 10.1002/eji.1830240818.


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 mgkg 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-gamma and IL-2 and to proliferate in response to polyclonal mitogenic stimulation with concanavalin A.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology
  • Female
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / pathology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred NOD
  • Receptors, Interleukin-1 / chemistry
  • Receptors, Interleukin-1 / immunology
  • Receptors, Interleukin-1 / physiology*
  • Spleen / cytology


  • Blood Glucose
  • Interleukin-2
  • Receptors, Interleukin-1
  • Interferon-gamma