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

Pancreas. 2003 May;26(4):e99-104. doi: 10.1097/00006676-200305000-00021.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antigens, Differentiation / analysis
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / prevention & control*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Immunohistochemistry
  • Insulin / analysis
  • Insulin / metabolism
  • Insulin Secretion
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-4 / blood
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pentoxifylline / analogs & derivatives*
  • Pentoxifylline / therapeutic use*
  • Random Allocation
  • Streptozocin / administration & dosage
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antigens, Differentiation
  • Insulin
  • Tumor Necrosis Factor-alpha
  • monocyte-macrophage differentiation antigen
  • Interleukin-10
  • Interleukin-4
  • Streptozocin
  • Interferon-gamma
  • lisofylline
  • Pentoxifylline