Abstract:
INTRODUCTION:Proinflammatory cytokines play an important role in the development of type 1 diabetes. Lisofylline (LSF) is a novel anti-inflammatory compound that specifically inhibits proinflammatory cytokine production and action. AIM:To investigate the effect of LSF on diabetes prevention. METHODOLOGY:A mouse with diabetes induced by multiple low doses of streptozotocin (STZ) can be used as an animal model for type 1 diabetes. In this study, we used this method to induce diabetes in C57BL/6J mice. The daily LSF treatment started 5 days before STZ injections and lasted for 2 weeks. The incidence of diabetes was monitored. Insulin secretion was assessed in pancreatic islets isolated from experimental mice. Cytokine production was measured in mouse sera. Islet apoptosis was assessed quantitatively. RESULTS:In LSF-treated mice, there was a significant reduction of diabetes incidence (25% vs. 91.6%). This protection was associated with suppression of systemic levels of IFN-gamma and TNF-alpha, inhibition of macrophage infiltration in islets, restoration of islet insulin secretion, and reduction of beta-cell apoptosis. CONCLUSIONS:This study suggests that treatment with LSF suppresses proinflammatory cytokines and protects beta-cells from inflammation. LSF may be useful for prevention of type 1 diabetes and other disorders associated with excessive proinflammatory cytokines.
journal_name
Pancreasjournal_title
Pancreasauthors
Yang Z,Chen M,Fialkow LB,Ellett JD,Wu R,Nadler JLdoi
10.1097/00006676-200305000-00021subject
Has Abstractpub_date
2003-05-01 00:00:00pages
e99-104issue
4eissn
0885-3177issn
1536-4828journal_volume
26pub_type
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