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


OBJECTIVE
To investigate the effect of LSF on diabetes prevention.


METHODS
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.
Yang
Zandong
Z
Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
Chen
Meng
M
Fialkow
Lawrence B
LB
Ellett
Justin D
JD
Wu
Runpei
R
Nadler
Jerry L
JL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000943:Antigens, Differentiation / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D000078790:Insulin Secretion; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011897:Random Allocation; D013311:Streptozocin / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000943:Antigens, Differentiation; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; C036763:monocyte-macrophage differentiation antigen; D016753:Interleukin-10; D015847:Interleukin-4; D013311:Streptozocin; D007371:Interferon-gamma; C025189:lisofylline; D010431:Pentoxifylline