Effects of technetium-99 methylenediphosphonate on cytokine-induced activation of retro-ocular fibroblasts from patients with Graves' ophthalmopathy.

Objective To explore the effects of technetium-99 methylenediphosphonate (Tc-99-MDP) on cell proliferation, hyaluronic acid (HA) synthesis and the expressions of human leucocyte antigen-DR (HLA-DR), intercellular adhesion molecule-1 (ICAM-1) on cultured retro-ocular fibroblasts (RFs) from patients with Graves' ophthalmopathy. Methods After two to seven passages, cultured RFs were incubated for 72 h with interferon-gamma (100 U/ml), interleukin-1 (100 U/m1) or tumour necrosis factor-alpha (100 U/ml) in the presence of Tc-99-MDP. Flow cytometry was used to investigate the expression of HLA-DR and ICAM-1. RF proliferation was assessed by H-3-thymidine incorporation assay. HA synthesis was measured by radioimmunoassay. Results At base conditions, the percentage of positive cells of HLA-DR and ICAM-1 on RFs was 6.70 +/- 3.06% and 5.29 +/- 3.02%, respectively, and the synthesis of HA was 337.8 +/- 42.7 ng/ml. Compared with basal values, 72-h incubation with cytokine significantly enhanced the expression of HLA-DR and ICAM-1, and HA synthesis. Tc-99-MDP (1 ng/ml) had little effect on cytokine-induced HLA-DR and ICAM-1 expression, and HA synthesis. When the concentration ranged from 10 to 100 ng/ml, Tc-99-MDP inhibited cytokine-induced RF activation in a dose-dependent manner. Tc-99-MDP also inhibited the proliferation of RFs in a dose-dependent manner. It was also found that Tc-99-MDP had the same effect on cytokine-induced RFs and skin fibroblasts from patients with normal individual conditions. Conclusions Tc-99-MDP could inhibit cytokine-induced activation of RFs derived from patients with Graves' ophthalmopathy. Nucl Med Commun 32:142-146 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Nuclear Medicine Communications 2011, 32:142-146