Horm Metab Res 2006; 38(3): 167-171
DOI: 10.1055/s-2006-925221
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Transient Chemokine Receptor Blockade does not Prevent, but may Accelerate Type 1 Diabetes in Prediabetic NOD Mice

C.  Seifarth1 , M.  Mack2 , S.  Steinlicht1 , E.-G.  Hahn1 , T.  Lohmann1, 3
  • 1Medizinische Klinik 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Ulmenweg 18, Erlangen, Germany
  • 2Klinikum der Universität Regensburg, Innere Medizin II, Regensburg, Germany
  • 3Current affiliation: Medizinische Klinik, Städtisches Krankenhaus Dresden-Neustadt
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Publikationsverlauf

Received 8 August 2005

Accepted after revision 13 December 2005

Publikationsdatum:
27. April 2006 (online)

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Abstract

The influx of autoreactive lymphocytes into the site of an autoimmune inflammation is mediated by certain chemokines. Autoimmune insulitis in type 1 diabetes is viewed as the result of destructive Th-1-cells and their corresponding antigen-presenting cells infiltrating the pancreatic islets. Blocking the chemokine receptors that mediate a Th-1-reaction has been shown to reduce autoimmunity in other experimental autoimmune disorders. We used the NOD mouse model to investigate the potency of anti-CCR2 and anti-CCR5 antibodies to inhibit the influx of Th-1-cells into the pancreatic islets, thus preventing diabetes onset. Eleven-week-old female NOD mice were treated with 500 µg of a monoclonal anti-CCR5 or anti-CCR2 or an isotype control antibody every third day over two weeks. We did not observe any preventive effect in either treatment group, but accelerated diabetes onset in the anti-CCR5 treated group. The number of autoantigen-specific Th-1-cells detected in the two treated groups was not reduced, but increased in the anti-CCR5 group. Redundancy within the chemokine system may account for this lack of prevention, or the intervention may have come too late in the disease process. Furthermore, blocking Th-1 chemokine receptors in the late autoimmune process may also inhibit regulatory T-cells, thus accelerating rather than preventing the disease.