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.
|Number of pages||4|
|Journal||British Journal of Ophthalmology|
|Publication status||Published - May 2011|
- Antibodies, Monoclonal/therapeutic use
- Antibodies, Monoclonal, Humanized
- Gene Expression Regulation/immunology
- Graves Ophthalmopathy/drug therapy
- Hyaluronic Acid/biosynthesis
- Imatinib Mesylate
- Piperazines/therapeutic use
- Pyrimidines/therapeutic use
- RNA, Messenger/biosynthesis
- Tissue Culture Techniques/methods
- Tumor Necrosis Factor-alpha/metabolism