Low dose streptozotocin-induced diabetes in mice: reduced IL-2 production and modulation of streptozotocin-induced hyperglycemia by IL-2.
The possible role of interleukin 2(IL-2) in the pathogenesis of multiple low dose streptozotocin (Sz)-induced diabetes in mice was analysed. Spleen cells from diabetic male C57Bl/6 mice showed diminished mitogen-induced IL-2 production as determined by bioassay using the IL-2-dependent T-cell line CTLL-2. In parallel the proliferative response was reduced. Systemic daily administration of human recombinant IL-2 for 3 weeks had dose-dependent effects on the development of hyperglycemia in Sz-treated (5 x 40 mg) mice: while IL-2 at doses of 1 x 2, 1 x 10, 2 x 10 micrograms/kg body weight caused partial suppression of hyperglycemia, higher doses (2 x 20, 2 x 40 micrograms/kg) had an enhancing effect. Treatment with the lowest dose (1 x 1 micrograms/kg) or with a control preparation from bacteria (2 x 10 micrograms/kg) did not significantly alter the course of diabetes. Effects of IL-2 were similar when treatment was started concomitantly with or only after streptozotocin injections. This observation argues against the direct interaction between IL-2 and streptozotocin but suggests modulation of immune reactivity by IL-2. Our findings of decreased mitogen-stimulated IL-2 production by splenic lymphocytes, and the disease-modulating effect of IL-2 in the low-dose streptozotocin diabetes extend our previous observations in spontaneously diabetic BB rats and further support the notion of an involvement of IL-2 in the control of autoimmune diseases.
Burkart
V
V
Diabetes Research Institute, Düsseldorf, F.R.G.
Zielasek
J
J
Kantwerk-Funke
G
G
Hibbe
T
T
Schwab
E
E
Kolb
H
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000209:etiology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006943:Hyperglycemia / Q000209:etiology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013311:Streptozocin
D007376:Interleukin-2; D011994:Recombinant Proteins; D013311:Streptozocin