Lisofylline: a potential lead for the treatment of diabetes.
Lisofylline (LSF), a synthetic modified methylxanthine, was originally designed and tested as an agent to reduce mortality during serious infections associated with cancer chemotherapy. Experimental studies and several clinical trials showed that LSF inhibited the generation of phosphatidic acid and free fatty acids. LSF also blocked the release of pro-inflammatory cytokines in oxidative tissue injury, in response to cancer chemotherapy and in experimental sepsis. Recent research has revealed a new potential to extend the therapeutic application of LSF especially for diabetes mellitus. These new studies demonstrate multiple actions of LSF in the regulation of immune cell function and autoimmune response by inhibition of IL-12 signalling and cytokine production. Supporting the new potential for LSF is the discovery of beneficial effects in protecting pancreatic beta cells and in preventing autoimmunity. In this article, these new observations about LSF are reviewed and a strategy proposed for using this compound in new clinical applications. LSF may, thus, have therapeutic value in the prevention of autoimmune disorders, including Type 1 diabetes, and autoimmune recurrence following islet transplantation, and in preservation of beta cell functional mass during islet isolation.
Yang
Zandong
Z
Department of Internal Medicine, Diabetes and Hormone Center of Excellence, Division of Endocrinology and Metabolism, University of Virginia, P.O. Box 801413, Charlottesville, VA 22908, USA. zy4q@virginia.edu
Chen
Meng
M
Nadler
Jerry L
JL
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
C025189:lisofylline; D010431:Pentoxifylline