Effects of IL-1 on hematopoietic progenitors after myelosuppressive chemoradiotherapy.
Recently it has been recognized that IL-1 plays an important role in hematopoietic regulation. Administration of 5-fluorouracil (5-FU) to mice causes prolonged neutropenia. rHIL-1 injected to mice after 5-FU, accelerated the recovery of hematopoietic progenitors and blood neutrophils. The combination of rhIL-1 and rhG-CSF reduced the neutropenic period significantly. Sublethal irradiation of mice induced profound neutropenia for 3 weeks which was associated with 80% mortality. Administration of rhIL-1 20 hours prior to or 2 hours post irradiation resulted in a significantly improved survival and rapid recovery of the neutrophil count. IL-1 administered alone or in combination with other colony stimulating factors to spontaneous breast tumor bearing mice following 5-FU therapy resulted in a rapid recovery of neutrophils, improved survival, and markedly reduced the tumor mass. Experiments in primates demonstrated that rhIL-1 administered to 5-FU treated animals shortened the neutropenic period from 30 to 17 days and increased the number of marrow progenitors responsive to other CSFs. Prolonged administration of IL-1 (14 days) to these animals resulted in a delayed neutrophil recovery as compared to animals receiving short courses of IL-1. rhIL-1 administered to primates receiving marrow grafts after lethal irradiation, did not result in rapid hematopoietic recovery. In humans, studies with CD-34 positive marrow cells showed that IL-1 had a radioprotective effect on a committed and early marrow progenitors. These data show the therapeutic potential of IL-1 in the treatment of chemoradiotherapy induced myelosuppression.
Laver
J
J
Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York.
Abboud
M
M
Gasparetto
C
C
Gillio
A
A
Smith
C
C
O'Reilly
R J
RJ
Moore
M A
MA
D000818:Animals; D018952:Antigens, CD34; D000943:Antigens, Differentiation / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells; D003131:Combined Modality Therapy; D064420:Drug-Related Side Effects and Adverse Reactions; D005472:Fluorouracil / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy; D011878:Radiotherapy / Q000009:adverse effects*
D018952:Antigens, CD34; D000943:Antigens, Differentiation; D007375:Interleukin-1; D005472:Fluorouracil