Transgenic expression of interleukin 10 in the pancreas renders resistant mice susceptible to low dose streptozotocin-induced diabetes.
Transgenic mice expressing interleukin 10 (IL-10) within the beta cells of the pancreas were used to assess the role of this cytokine in the development of diabetes following low-dose streptozotocin treatment. Nontransgenic mice injected with low doses of streptozotocin were largely resistant to the induction of hyperglycaemia; that is, average blood glucose values, although above mean blood glucose levels of buffer-injected controls, did not exceed 14 mmol/l. In sharp contrast, IL-10 transgenic mice exhibited significant sensitivity to the diabetogenic actions of streptozotocin resulting in a mean blood glucose level of 21.6 mmol/l at the end of the 56-day study period. Histological analysis of pancreata from streptozotocin-injected transgenic mice revealed severe insulitis and destruction of pancreatic beta cells, whereas their streptozotocin-injected nontransgenic littermates remained completely insulitis-free. According to immunocytochemical analysis, the pancreatic inflammatory infiltrates of streptozotocin-injected transgenic mice contained CD4+ and CD8+ T lymphocytes, B lymphocytes and macrophages. Furthermore, various adhesion molecules, the co-stimulatory molecule B7-1 and the Ia antigen could be detected. Splenocytes from streptozotocin-injected transgenic mice did not transfer disease to irradiated syngeneic nontransgenic recipients, suggesting that the presence of IL-10 in streptozotocin-injected mice had a general immunostimulatory effect but did not lead to the activation of beta cell-specific T cells. Our data suggest a critical role for IL-10 in the development of diabetes in vivo despite its established immunosuppressive activities in vitro.
Mueller
R
R
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Lee
M S
MS
Sawyer
S P
SP
Sarvetnick
N
N
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001786:Blood Glucose / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D006943:Hyperglycemia / Q000139:chemically induced / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology* / Q000378:metabolism; D013311:Streptozocin
D001786:Blood Glucose; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D013311:Streptozocin