Summary.The improvement in sickle cell disease (SCD) children receiving cromolyn sodium therapy prompted us to investigate its antisickling activity in vitro. The number of sickle cells was determined in deoxygenated blood samples from 15 children with severe SCD. At the eight concentrations tested, cromolyn sodium exhibited a significantly higher activity than pentoxifylline, the standard compound.Therefore cromolyn sodium would appear to be an interesting candidate for SCD therapy and deserves further in vivo investigations.Keywords: cromolyn sodium, antisickling activity, corpuscular indices.New approaches have been recently proposed for the treatment of SCD such as bone marrow transplantation or HbF synthesis modulation . Ancillary treatments aimed at the correction of secondary erythrocytic or rheological abnormalities also deserve renewed interest.At our centre, allergy had been previously diagnosed in 43% of SCD children. Treatment by allergen eviction and anti-allergic drugs such as cromolyn sodium was followed by a dramatic reduction of vaso-occlusive crises and of recurrent airway infections in some children (Toppet et al, 1993). Therefore we initiated an in vitro study of the possible effect of cromolyn sodium on sickling using as standard pentoxifylline whose antisickling activity, mediated by calcium L channels blockade, is well established (Ellory et al, 1994).
MATERIALS AND METHODSBlood collection. Samples from 15 African children with severe SCD were collected. All the patients except two had a previous history of multiple recurrent vaso-occlusive crises. Seven of them were on hydroxyurea therapy at time of the study.The Hospital Ethics Committee approved the study protocol. Oral informed consent was obtained from patients and their legal guardians. Erythrocytes preparation. 5 ml of venous blood drawn in EDTA-rinsed tubes were processed within 2 h of collection. The red cells were washed three times in a phosphatebuffered saline (PBS, pH 7·40) and suspended in twice their volume of PBS.Drugs and control solutions. Stock-solutions of pentoxifylline (3,7-dihydro-3,7-dimethyl-1-(5-oxohexyl)-1H-purine-2,6-dione, Hoechst Roussel, Bruxelles, Belgium) and of cromolyn sodium (5,5 0 -[(hydroxy-1,3-propanediyl)bis-(oxy)[bis] 4-oxo-4H-1-benzopyran-2-carboxylic acid, disodium salt], Sigma Chemie, Bornem, Belgium) were prepared in PBS and kept at 4ЊC. PBS was used as control.Deoxygenating device. The apparatus included a gas tank, a 250 ml glass flask half-filled with water, a 10 ml glass tube, a flexible duct and a water bath maintained at 37ЊC. All the containers were stoppered with their upper part allowing inlet and outlet of the gas (5% CO 2 in N 2 ) which was prehumidified by bubbling in the flask. After incubation for 60 min, 150 ml of the erythrocytes suspension to which had been added 150 ml of the tested drug solution, were transferred into the tube and the humidified gas was bubbled in the preparation for 30 min at a constant flow rate of 3 ml/ min. The lower part of the flask and the tube were im...