The novel anti-inflammatory compound, lisofylline, prevents diabetes in multiple low-dose streptozotocin-treated mice.

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

Pancreas

journal_title

Pancreas

authors

Yang Z,Chen M,Fialkow LB,Ellett JD,Wu R,Nadler JL

doi

10.1097/00006676-200305000-00021

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

e99-104

issue

4

eissn

0885-3177

issn

1536-4828

journal_volume

26

pub_type

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