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To examine the role of endogenous MIF in the pathogenesis of type 1 diabetes (TID) we evaluated the effects of administration of neutralizing anti\u2010MIF antibodies to NOD mice with accelerated forms of diabetes induced by injection of cyclophosphamide or by transfer of diabetogenic spleen cells. Both accelerated forms of diabetes were markedly reduced by anti\u2010MIF antibody. Furthermore, MIF\u2010deficient (MIF<jats:sup>\u2212\/\u2212<\/jats:sup>) mice were less susceptible to the induction of immunoinflammatory diabetes, insulitis and apoptosis within the endocrine pancreas by multiple low doses of streptozotocin (MLD\u2010STZ) than genetically matched wild type (WT) mice. MIF deficiency resulted in lower proliferation and lymphocyte adhesion, as well as reduced production from the spleens and peritoneal cells of a variety of inflammatory mediators typically associated with development of the disease including IL\u201012, IL\u201023, TNF\u2010\u03b1, and IL\u20101\u03b2. Furthermore, MIF deletion affected the production of IL\u201018, TNF\u2010\u03b1, IL\u20101\u03b2, and iNOS in the islets of Langerhans. These data, along with the higher expression of IL\u20104 and TGF\u2010\u03b2 observed in the periphery and in the pancreas of MLD\u2010STZ\u2010challenged MIF<jats:sup>\u2212\/\u2212<\/jats:sup> mice as compared to WT controls suggest that MIF deficiency has induced an immune deviation towards protective type 2\/3 response. These results suggest that MIF participates in T1D by controlling the functional activity of monocytes\/macrophages and T cells and modulating their secretory capacity of pro\u2010 and anti\u2010inflammatory molecules. J. Cell. Physiol. 215: 665\u2013675, 2008. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21346","type":"journal-article","created":{"date-parts":[[2007,12,6]],"date-time":"2007-12-06T20:48:44Z","timestamp":1196974124000},"page":"665-675","source":"Crossref","is-referenced-by-count":77,"title":["Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes 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