TY - JOUR
T1 - Effect of antiviral drugs and hematopoietic growth factors on in vitro erythropoiesis
AU - Weinberg, Rona S.
AU - Chusid, Eileen D.
AU - Galperin, Yelena
AU - Thomson, Joann C.
AU - Cheung, Tony
AU - Sacks, Henry S.
PY - 1998/1
Y1 - 1998/1
N2 - Background: The purpose of these studies was to improve our understanding of nucleoside analog, antiviral, drug-induced anemia in HIV infection. Methods: Peripheral blood erythroid progenitor cells (BFU-E) from HIV-positive (HIV+) patients and normal donors were compared in methylcellulose cultures with erythropoietin, with and without antiviral drugs, and with and without the hematopoietic growth factors, stem cell factor (SCF), hemin, and interleukin-3 (IL-3). Results: Normal numbers of BFU-E-derived colonies were observed in cultures from HIV+ patients (mean ± 1 SD BFU-E/105 cells plated: normal = 14.1 ± 7.9, HIV+ = 17.2 ± 14.2, p = 0.39). The antiviral drugs zidovudine (AZT), dideoxyinosine (ddI), and diedehydrodideoxythymidine (d4T) all inhibited erythroid colonies in HIV+ and normal cultures. AZT was the most erythropoietically inhibitory drug (AZT ID50, mean ± 1 SD for normal cultures = 2.64 ± 4.15 μM, for HIV+ cultures = 6.28 ± 10.79 μM, p = 0.24). Hematologic toxicity was less with ddI and d4T. However, doses of ddI and d4T ≤ 10 μM inhibited colony growth in 9/14 and 8/12 cultures, respectively, from HIV+ patients. Conclusions: Stem cell factor (SCF), hemin, and interleukin-3 (IL-3) increased colony growth in HIV+ and normal cultures. In control cultures, hematopoietic growth factors added singly increased growth 1.3- to 8-fold. Hematopoietic growth factors increased growth even in cultures containing antiviral drugs. In some instances growth factors restored growth to control levels. SCF, hemin, and IL-3 were most effective when combined.
AB - Background: The purpose of these studies was to improve our understanding of nucleoside analog, antiviral, drug-induced anemia in HIV infection. Methods: Peripheral blood erythroid progenitor cells (BFU-E) from HIV-positive (HIV+) patients and normal donors were compared in methylcellulose cultures with erythropoietin, with and without antiviral drugs, and with and without the hematopoietic growth factors, stem cell factor (SCF), hemin, and interleukin-3 (IL-3). Results: Normal numbers of BFU-E-derived colonies were observed in cultures from HIV+ patients (mean ± 1 SD BFU-E/105 cells plated: normal = 14.1 ± 7.9, HIV+ = 17.2 ± 14.2, p = 0.39). The antiviral drugs zidovudine (AZT), dideoxyinosine (ddI), and diedehydrodideoxythymidine (d4T) all inhibited erythroid colonies in HIV+ and normal cultures. AZT was the most erythropoietically inhibitory drug (AZT ID50, mean ± 1 SD for normal cultures = 2.64 ± 4.15 μM, for HIV+ cultures = 6.28 ± 10.79 μM, p = 0.24). Hematologic toxicity was less with ddI and d4T. However, doses of ddI and d4T ≤ 10 μM inhibited colony growth in 9/14 and 8/12 cultures, respectively, from HIV+ patients. Conclusions: Stem cell factor (SCF), hemin, and interleukin-3 (IL-3) increased colony growth in HIV+ and normal cultures. In control cultures, hematopoietic growth factors added singly increased growth 1.3- to 8-fold. Hematopoietic growth factors increased growth even in cultures containing antiviral drugs. In some instances growth factors restored growth to control levels. SCF, hemin, and IL-3 were most effective when combined.
KW - AZT
KW - Erythropoiesis
KW - Hemin
KW - Stem cell factor
KW - d4T
KW - ddI
UR - http://www.scopus.com/inward/record.url?scp=0031963062&partnerID=8YFLogxK
M3 - Article
C2 - 9458678
AN - SCOPUS:0031963062
SN - 0027-2507
VL - 65
SP - 5
EP - 13
JO - Annals of Global Health
JF - Annals of Global Health
IS - 1
ER -