Whole orbital tissue culture identifies imatinib mesylate and adalimumab as potential therapeutics for Graves' ophthalmopathy

Leendert van Steensel, P Martin van Hagen, Dion Paridaens, Robert W A M Kuijpers, Willem A van den Bosch, Hemmo A Drexhage, Herbert Hooijkaas, Willem A Dik

Research output: Contribution to journalArticleResearchpeer-review


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.

Original languageEnglish
Pages (from-to)735-8
Number of pages4
JournalBritish Journal of Ophthalmology
Issue number5
Publication statusPublished - May 2011


  • Adalimumab
  • Antibodies, Monoclonal/therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Benzamides
  • Female
  • Gene Expression Regulation/immunology
  • Graves Ophthalmopathy/drug therapy
  • Humans
  • Hyaluronic Acid/biosynthesis
  • Imatinib Mesylate
  • Interleukin-6/biosynthesis
  • Male
  • Piperazines/therapeutic use
  • Pyrimidines/therapeutic use
  • RNA, Messenger/biosynthesis
  • Tissue Culture Techniques/methods
  • Tumor Necrosis Factor-alpha/metabolism


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