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 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.
Nicoletti
F
F
Second department of Medical Pathology and Metabolic Diseases, University of Catania, Italy.
Di Marco
R
R
Barcellini
W
W
Magro
G
G
Schorlemmer
H U
HU
Kurrle
R
R
Lunetta
M
M
Grasso
S
S
Zaccone
P
P
Meroni
P
P
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D017472:Receptors, Interleukin-1 / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D013154:Spleen / Q000166:cytology
D001786:Blood Glucose; D007376:Interleukin-2; D017472:Receptors, Interleukin-1; D007371:Interferon-gamma