J. Meletis et al 522 A.E. Tsantes et al Haema 2003; 6(4): 522-528 Original article The effect of theophylline on erythropoiesis: clinical implications for the obstructive respiratory syndromes Argirios E. Tsantes 1 , Stergios T. Tassiopoulos 2 , Stefanos Bonovas 1 , Ioanna Gligori 1 , Stefanos I. Papadhimitriou 1 , Georgios Giannikopoulos 3 , Dimitrios Loukopoulos 2 , John Meletis 2 1 Laboratory of Haematology, G. Gennimatas, Athens General District Hospital, 2 First Department of Internal Medicine, 3 First Department of Propedeutic Medicine, University of Athens, Medical School, Laikon General Hospital, Athens, Greece. Abstract. Long treatment with theophylline is often followed by a reduction of haemoglobin levels, which is usually ascribed to the antagonistic activity between theophylline and adenosine (ADO), which leads to decreased erythropoietin (EPO) synthesis. This view is not unanimously accepted. To evaluate the influence of theophylline on erythropoiesis in chronic obstructive pulmonary disease (COPD), the haematologic parameters and EPO values were estimated in 32 patients with COPD. Twelve of them had been treated with theophylline for at least 1 year; the other 20 patients had never received this drug. 34 sex- and age-matched healthy volunteers served as controls. We further studied the development of BFU-E-derived colonies in semisolid methylcellulose cultures in blood samples from 7 patients randomly selected from both groups. In addition, we studied the effects of theophylline on the erythroid cell development by adding this agent in erythroid cell cultures from 6 healthy volunteers at various concentrations. No significant differences were found in the haemoglobin and serum erythropoietin values between the 2 COPD groups (treated and untreated). Unlike untreated patients and controls, the serum of the theophylline-treated patients produced a significant growth inhibition of erythroid bursts (p<0.05); the in vitro use of theophylline showed a concentration dependent inhibition (p<0.001). The fact that the erythropoietin amount was consistently more than adequate for optimal erythropoietic development in culture dishes, suggests a direct inhibitory action of theophylline on erythropoiesis, possibly through the enhanced apoptosis induced by this drug in several other types of cells. The fact that the Hb levels did not show any significant differences implies the involvement of other factors both on the serum levels of the drug and on the erythropoietic response in each individual marrow. Key words: erythropoiesis  theophylline  obstructive respiratory syndromes * Correspondence: Argirios E. Tsantes, MD, Vasilikon 10 str., Athens 10442, Greece, Tel.:+30210.5154915, e-mail:atsantes@yahoo.com INTRODUCTION The erythropoietic response in hypoxaemic pa- tients with chronic obstructive pulmonary disease (COPD) is unpredictable 1-3 . Theophylline is included among the factors incriminated for this differentiated *The study was supported by the Greek Scholarships Foundation