Cytokine release by murine spleen cells following multiple low dose streptozotocin-induced diabetes and treatment with a TNFα transcriptional inhibitor

被引:20
作者
Thorvaldson, L [1 ]
Holstad, M [1 ]
Sandler, S [1 ]
机构
[1] Uppsala Univ, Ctr Biomed, Dept Med Cell Biol, SE-75123 Uppsala, Sweden
关键词
cytokine; mice; streptozotocin; TNF alpha; type; 1; diabetes;
D O I
10.1016/S1567-5769(03)00183-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We recently reported that administration of 9-[(1R, 3R)-trans-cyclopentan-3-ol] adenine (MDL 201,449A), a transcriptional inhibitor of TNFalpha decreased hyperglycemia in murine diabetes induced by multiple low doses of streptozotocin (MLDSTZ). In the present study, we first investigated if in vivo administration of MDL 201,449A in the MLDSTZ model affects cytokine release from cultured spleen cells. Secondly, we studied how MDL 201,449A affects cytokine release from normal cultured spleen cells. In all experiments, the mitogen concanavalin A (2 mug/ml) was added to the cultured spleen cells in order to enhance cytokine release. MLDSTZ treatment in vivo caused increased IFNgamma secretion, a decreased/retarded rate of increased TNFalpha accumulation, whereas IL-10 production was not altered compared to vehicle-treated mice. MDL 201,449A treatment of MLDSTZ mice did not affect cytokine release from spleen cells subsequently cultured in the absence of MDL 201,449A. We also studied cytokine release from normal spleen cells in the presence or absence of MDL 201,449A. Production of TNFalpha, IFNgamma and IL-10 was all suppressed by the drug. In groups where exposure to MDL 201,449A was discontinued, cytokine levels increased promptly and in the case of TNFalpha secretion, it exceeded the production from control cells. Our data suggest an enhanced Th1 cytokine secretion from spleen cells derived from MLDSTZ-treated mice. MDL 210,449A may be a potent inhibitor of cytokine secretion, albeit not completely selective for TNFalpha. However, when MDL 201,449A is withdrawn, there may be a rebound phenomenon of increased TNFalpha secretion. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码:1609 / 1617
页数:9
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