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Whole orbital tissue culture identifies imatinib mesylate and adalimumab as potential therapeutics for Graves' ophthalmopathy
  1. Leendert van Steensel1,
  2. P Martin van Hagen1,2,3,
  3. Dion Paridaens3,
  4. Robert W A M Kuijpers4,
  5. Willem A van den Bosch3,
  6. Hemmo A Drexhage1,
  7. Herbert Hooijkaas1,
  8. Willem A Dik1
  1. 1Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
  2. 2Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
  3. 3Rotterdam Eye Hospital, Rotterdam, The Netherlands
  4. 4Department of Ophthalmology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
  1. Correspondence to Dr Willem A Dik, Department of Immunology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands; w.dik{at}erasmusmc.nl

Abstract

Background and aims Biologicals and small inhibitory molecules are used to treat inflammatory diseases, but their efficacy varies upon clinical application. Using a whole orbital tissue culture system, we tested the potential efficacy of imatinib mesylate (a tyrosine kinase inhibitor that blocks platelet-derived growth factor (PDGF)-receptor, c-Abl and c-Kit activity) and adalimumab (an anti-TNF-α antibody) for the treatment of Graves' ophthalmopathy (GO).

Methods Orbital fat tissue from GO patients (n=10) was cultured with or without imatinib mesylate or adalimumab. PDGF-B and tumour necrosis factor (TNF)-α mRNA expression levels were determined in the primary orbital tissue, and interleukin (IL)-6 and hyaluronan were measured in tissue-culture supernatants.

Results Imatinib mesylate significantly (p=0.005) reduced IL-6 and hyaluronan production. The inhibition of hyaluronan production correlated positively and significantly (p<0.05) with the PDGF-B mRNA level in the primary tissue. Adalimumab also significantly (p=0.005) reduced IL-6 production. The amount of IL-6 inhibition correlated positively with the TNF-α mRNA level in the primary tissue, but this was not significant.

Conclusions Imatinib mesylate can be expected to reduce inflammation and tissue remodelling in GO, while adalimumab can be mainly expected to reduce inflammation. This in vitro tissue-culture model may, in future, prove valuable to test novel therapeutics for their presumed effect in GO as well as in other inflammatory diseases.

  • Graves'
  • ophthalmopathy
  • therapy
  • imatinib mesylate
  • adalimumab
  • orbit
  • immunology
  • inflammation
  • treatment medical
  • experimental & laboratory

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Footnotes

  • Funding ‘Stichting Wetenschappelijk Onderzoek Oogziekenhuis’ (SWOO 2007-01; LvS), Schiedamse Vest 180, 3011 BH Rotterdam; Prof. dr. Henkes Stichting, Schiedamse Vest 180, 3011 BH Rotterdam; Nederlandse Vereniging van Graves' Patienten (NVGP), Stationsplein 79 G, 3811 MH Amersfoort.

  • Competing interests PMvH is consultant for Abbott and Novartis Pharma (The Netherlands).

  • Ethics approval Ethics approval was provided by the institutional ethical review board of Erasmus MC, University Medical Center, Rotterdam.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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