Fiorelli G, Carandini D, Gaviraghi A, Velati C, Lazzarin A, Galli M, Cappellini MD; International Conference on AIDS.
Int Conf AIDS. 1992 Jul 19-24; 8: B213 (abstract no. PoB 3732).
Inst Int Med and Med Physiopath, University of Milan, Italy.
Zidovudine (AZT), the most effective drug in the treatment of HIV infected patients, is responsible for several side effects, the most important of which is pancytopenia. Anemia is the primary manifestation, often requiring transfusions and limiting the AZT treatment; Recombinant Human Erythropoietin (rHEpo) has been used to treat patients developing severe anemia while receiving Zidovudine, nevertheless as many as 30-40% of HIV infected patients treated with rHEpo failed to correct the hemoglobin levels. Several other cytokines are known to be active in erythropoiesis. The aim of this work was to prove the inhibition by AZT of normal BFU-E growth and to check the capacity of IL-3 and Human Stem Cell Factor (SCF) to modify the AZT inhibitory effect. BFU-E from peripheral blood of 10 normal volunteers (age range: 20-40 yr), after Ficoll-Hypaque sedimentation, were cultured in alpha-metylcellulose with 4U rHEpo, according to the Iscove method minor modifications. AZT was added to the culture at the final concentrations of 0.1 ug/ml, 0.2 ug/ml and 0.5 ug/ml, respectively. IL-3 (Genzyme Corporation, USA) was added with and without AZT at final concentrations of 75, 115, and 150 ng/ml. Human recombinant SCF (Genzyme) was added alone and in presence of AZT with and without IL-3 at concentrations of 10, 100 and 1000 ng/ml. The BFU-E colonies were scored at day 14 of culture by a light inverted microscope and the cells forming the colonies were counted, after bursts disgregation in cold saline buffer, by a coulter counter. The BFU-E were reduced in the presence of increasing amounts of AZT (the percentages of colonies were: 69.4, 57.2 and 48.7 of basal value (100%) respectively: p less than 0.001). The cells number per colony was also significantly reduced (62, 46, 31% of basal: p less than 0.01). IL-3 and SCF stimulate independently the BFU-E growth over 150%. The increase was statistically significant (p less than 0.001). In presence of AZT, IL-3 and/or SCF significantly alter the inhibitory effect of AZT on BFU-E growth in a dose-dependent manner. These data suggest that several cytokines could be used in association to EPO to correct the severe anemia of HIV infected patients.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Anemia
- Erythroid Progenitor Cells
- Erythropoiesis
- Erythropoietin
- Erythropoietin, Recombinant
- HIV Infections
- Humans
- In Vitro
- Interleukin-3
- Murine Acquired Immunodeficiency Syndrome
- Stem Cell Factor
- Zidovudine
Other ID:
UI: 102199177
From Meeting Abstracts