Peroxisome proliferator‐activated receptor gamma agonists in the prevention and treatment of murine systemic lupus erythematosus. Issue 3 (July 2014)

• Record Type: Journal Article
• Authors: Aprahamian, Tamar R.; Bonegio, Ramon G.; Weitzner, Zachary; Gharakhanian, Raffi; Rifkin, Ian R.
• Is Part Of: Immunology. Volume 142:Issue 3(2014:Jul.)
• Page Start: 363
• Page End: 373
• Publication Date: 2014-07
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12256
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12256-abs-0001"> <title>Summary</title> <p>Peroxisome proliferator‐activated receptor gamma (PPAR<italic>γ</italic>) agonists are known to have many immunomodulatory effects. We have previously shown that the PPAR<italic>γ</italic> agonist rosiglitazone is beneficial when used early in prevention of disease in murine models of systemic lupus erythematosus (SLE) and SLE‐related atherosclerosis. In this report, we demonstrate that another PPAR<italic>γ</italic> agonist, pioglitazone is also beneficial as a treatment for early murine lupus, indicating that this is a class effect and not agent‐specific. We further attempt to define the ability of PPAR<italic>γ</italic> agonists to ameliorate established or severe autoimmune disease using two mouse models: the MRL.<italic>lpr </italic>SLE model and the <italic>gld</italic>.apoE<sup>−/−</sup> model of accelerated atherosclerosis and SLE. We demonstrate that, in contrast to the marked amelioration of disease seen when PPAR<italic>γ</italic> agonist treatment was started before disease onset, treatment with rosiglitazone after disease onset in MRL.<italic>lpr</italic> or <italic>gld</italic>.apoE<sup>−/−</sup> mice had minimal beneficial effect on the development of the autoimmune phenotype; however, rosiglitazone treatment remained highly effective at reducing lupus‐associated atherosclerosis in <italic>gld</italic>.apoE<sup>−/−</sup> mice after disease onset or when mice were maintained on a high cholesterol Western diet. These results suggest that beneficial effects of PPAR<italic>γ</italic> agonists on the development of autoimmunity might be limited to the early stages of disease, but that atherosclerosis, a major cause of death in SLE patients, may be ameliorated even in established or severe disease.</p> </abstract>