Effect of pentoxifylline and glucocorticoids on peripheral blood mononuclear cells proliferation and apoptosis in Graves' ophthalmopathy
Anastasiya Hlazkova1, Irina Melnik1, Larissa Danilova1, Svetlana Kosmacheva2, Nataliya Goncharova2, Denis Antipovich1 & Janna Kirilenko1
The phosphodiesterase inhibitor pentoxifylline (PTX) is known to have immunomodulatory effects in some autoimmune diseases. The aim of our study was to assess the influence of glucocorticoids monotherapy and additive treatment with PTX on peripheral blood mononuclear cells (PBMC) proliferation and apoptosis in patients with Graves ophthalmopathy (GO).
Eighteen patients with GO and 28 healthy controls were investigated. GO patients were divided into two groups: A 10 patients treated with glucocorticoids, B 8 patients treated with glucocorticoids and PTX for 6 weeks. We assessed the proliferation of PBMC stimulated with phytohemagglutinin (PHA) 0.5 μg/ml, 10.0 μg/ml. Both spontaneous and PHA-induced three-day apoptosis was evaluated by flow cytometric analysis. 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, PHA 10.0 μg/ml, P<0.05). After treatment SI reduced in both groups, but significant differences observed in group B (PHA 0.5 μg/ml 19.91±10.68 vs 9.38±4.68, P<0.05; PHA 10.0 μg/ml 98.39±16.72 vs 53.53±8.62, P<0.05).There was a significant difference of stimulated apoptosis between GO patients and controls before treatment (P<0.001). Following 6 weeks of therapy apoptosis level increased in both groups of patients. However, the apoptosis value significantly increased after the combination therapy with PTX only (4.0±1.36 vs 21.0±7.42%, P< 0.05) in comparison with glucocorticoids monotherapy (3.4±1.45 vs 12.3±4.72%, P>0.05). Thus, our investigation indicates that PTX potentiate the effect of glucocorticoids on PBMC proliferation and apoptosis in GO patients.