title: Macrophage migration inhibitory factor and development of type-1 diabetes in non-obese diabetic mice.
abstract: OBJECTIVE
  T-cell activation by specific antigen has been found to increase macrophage migration inhibitory factor (MIF) expression, indicating its role as an important feature of T-cell activation in vitro and in vivo. To date, the potential role of MIF in the development of autoimmune-mediated diabetes mellitus has not been studied.
  
  
  METHODS
  MIF-mRNA expression in splenic lymphocytes of spontaneously diabetic non-obese diabetic (NOD) mice (n=6), cyclophosphamide-treated NOD mice (n=6), 14-day-old non-diabetic NOD mice (n=7) and C57/Bl6 control mice (n=6) was monitored using an internally standardised competitive reverse transcription-polymerase chain reaction, and the MIF-protein levels were determined using Western blot analysis. In addition, the impact of intraperitoneally administered recombinant MIF-protein treatment on diabetes incidence in NOD mice was evaluated.
  
  
  RESULTS
  MIF-mRNA expression was markedly increased in splenic lymphocytes of spontaneously diabetic NOD mice as well as in 8-week-old NOD mice treated with cyclophosphamide compared with 2-week-old non-diabetic NOD and healthy C57BL/6 control mice. Western blot analyses showed decreased lymphocytic MIF-protein content in diabetic as well as in cyclophosphamide-treated animals compared with 2-week-old non-diabetic NOD and healthy C57BL/6 mice, probably as a consequence of increased protein secretion. Furthermore, treatment of NOD mice with recombinant MIF-protein at 25 microg twice a week, from age 6 to 11 weeks, led to an increased diabetes incidence (86%; n=7) compared with untreated control groups (55%; n=20) at week 34.
  
  
  CONCLUSIONS
  In this study, we report for the first time that MIF-mRNA expression in splenic lymphocytes is up-regulated during development of cell-mediated diabetes in non-NOD mice. The data of our preliminary study suggest a possible role of MIF in autoimmune-inflammatory events, such as type-1 diabetes and also that anti-MIF therapeutic strategy might serve to attenuate autoimmune processes.
authors.affiliation: Department of Medicine I, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany. dr_bojunga@web.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Bojunga
authors.forename: Klaus
authors.initials: K
authors.lastname: Kusterer
authors.forename: Michael
authors.initials: M
authors.lastname: Bacher
authors.forename: Ralf
authors.initials: R
authors.lastname: Kurek
authors.forename: Klaus-Henning
authors.initials: KH
authors.lastname: Usadel
authors.forename: Heiner
authors.initials: H
authors.lastname: Renneberg
mesh_terms: D017668:Age of Onset; D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011236:Prediabetic State; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013156:Splenectomy
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger