ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2009) 20 P61

Influence of pentoxifylline on peripheral blood mononuclear cells proliferation and apoptosis in Graves' ophthalmopathy

Irina Melnik1, Anastasiya Hlazkova1, Svetlana Kosmacheva2, Natallia Goncharova2, Larisa Danilova1 & Aleksey Romanovskiy1

1Belarussian Medical Academy of Post-Graduate Education, Minsk, Belarus; 2Republican Scientific and Practic Center for Hematology and Transfusiology, Minsk, Belarus.

Pentoxifylline (PTX), a phosphodiesterase inhibitor, has a positive therapeutic effect in some autoimmune diseases due to immunomodulatory action.

The aim of the study was to assess the influence of PTX on apoptosis and peripheral blood mononuclear cells (PBMC) proliferation in patients with Graves’ ophthalmopathy (GO).

Twenty-four patients with GO and 32 healthy controls were investigated. GO patients were divided into two groups: I – 14 patients treated only with methimazole, II – 10 patients treated with methimazole and PTX. PTX retard dosage form was prescribed in a dose of 600 mg once daily/6 weeks. We assessed the proliferation of PBMC stimulated with phytohemagglutinin (PHA) 0.5 μg/ml, 10.0 μg/ml, PMA, PWM. Both spontaneous and PHA-induced three-day apoptosis was evaluated by flow cytometric analysis. There was a significant difference of stimulated apoptosis between GO patients and controls before treatment (P<0.0001). Following 6 weeks of therapy with pentoxifylline, the apoptosis value significantly increased among patients group II (3.54±1.16 vs 21.99±7.42%, P<0.05). There was no significant difference in the levels of apoptosis in group I after treatment (4.23±1.21 vs 8.6±4.12%, P>0.05). Results of proliferation assay being expressed as stimulation index (SI). Mean SI for patients with GO prior to therapy was significantly higher then controls (PHA 0.5 μg/ml, P<0.01; PHA 10.0 μg/ml, P<0.05). After treatment SI decreased in both group of patients. However, significant differences observed in group II only (PHA 0.5 μg/ml 22.34±4.82 vs 7.12±2.6, P<0.05; PHA 10.0 μg/ml 98.83±10.28 vs 53.57±4.31, P<0.001; PWM 39.04±6.33 vs 24.68±3.96, P<0.05).

In conclusion, we have demonstrated significant increasing of apoptosis and profound inhibitory effect of PTX on mitogen-induced proliferation of PBMC in GO patients. This results showed the potential of PTX in the management of GO.

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