[Demonstration of a protector effect of interleukin-1 against hematologic toxicity of azidothymidine (AZT)].
3'-azido-3'-deoxythymidine (Azidothymidine or AZT) has attained wide critical utility in the treatment of acquired immunodeficiency syndrome (AIDS). Unfortunately, treatment with AZT is associated with the development of severe hematopoietic toxicity. The AZT sensitivity of marrow progenitors was different with an IC 50 of 10(-8) M and 10(-6) M for respectively BFU-E and CFU-GM/GEMM. Data reported here show that recombinant human interleukin-1 alpha (IL-1 alpha), a pleiotropic cytokine, was demonstrated to be efficient to protect normal human as well as murine hematopoietic progenitors (CFU-GM, CFU-GEMM and BFU-E) from the toxic effect of AZT. The maximal effect was observed with 30 U/ml (Human cells) or 100 U/ml (murine cells) IL-1 alpha for BFU-E and CFU-GM/GEMM, with a marked effect at 1 U/ml. The results demonstrate that marrow progenitors respond differently to AZT and point out the potential efficacy of IL-1 alpha to enhance the proliferation of hematopoietic stem cells treated with growth factors (IL-3, erythropoietin) and to minimize the hematopoietic toxicity associated with AZT treatment.
Arock
M
M
Laboratoire d'Hématologie, Faculté de Pharmacie, Paris.
Dedenon
A
A
Damais
C
C
Averlant
G
G
Guillosson
J J
JJ
D000328:Adult; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D015215:Zidovudine / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D007375:Interleukin-1; D015215:Zidovudine
Mise en évidence d'un effet protecteur de l'Interleukine-1 vis-à-vis de la toxicité hématologique de l'azidothymidine (AZT).