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Pancreas. 2003 May;26(4):e99-104.

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

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  • 1Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.

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.

PMID:
12717280
[PubMed - indexed for MEDLINE]
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