Effects of interleukin-1 on hematopoietic progenitors: Evidence of stimulatory and inhibitory activities in a primate model Journal Article
| Authors: | Gasparetto, C.; Laver, J.; Abboud, M.; Gillio, A.; Smith, C.; O'Reilly, R. J.; Moore, M. A. S. |
| Article Title: | Effects of interleukin-1 on hematopoietic progenitors: Evidence of stimulatory and inhibitory activities in a primate model |
| Abstract: | The effects of recombinant human interleukin-1 rhIL-1 beta (rhIL-1b) on hematopoietic recovery following chemotherapy in a primate model were investigated. Cynomolgus monkeys received 1 μg/kg/day rhIL-1b intravenously for 2, 7, and 14 days following 5-Fluorouracil (5-FU) treatment (75 mg/kg x 2 days). Compared with controls, a significantly shortened time to achieve an absolute neutrophil (ANC) count over 500/μL was observed in animals receiving 2- and 7-day courses of rhIL-1b (17 v 30 days), while animals receiving a 14-day course of rhIL-1b achieved an ANC over 500/μL by 23 days. Concomitantly, a marked increase in granulocyte-macrophage colonies (CFU-GM) was observed at 14 days following 5-FU in animals receiving 2- and 7-day rhIL-1b courses. In animals receiving a 14-day rhIL-1b course, a significant increase in CFU-GM relative to control was not seen until 21 days post 5-FU. Utilizing a serum-free colony assay system, a 50% inhibition of normal marrow CFU-GM growth was observed with the addition of sera obtained on day 9 post 5-FU from animals receiving rhIL-1b for 14 days. Sera obtained at any time from animals receiving 2- and 7-day rhIL-1b treatment did not show any growth inhibition. Addition of antibodies to TNFa to the coculture assay abrogated the CFU-GM growth inhibition. TNFa levels in sera with the inhibitory activity was relatively high (918 pg/mL). Our data indicate that rhIL-1b enhances hematopoietic recovery following 5-FU if administered for short periods of time (< 7 days), whereas prolonged administration has a counterproductive effect that is due in part to the induction of TNFa production. |
| Keywords: | fluorouracil; nonhuman; animal cell; animal; bone marrow; interleukin 1beta; cell culture; recombinant proteins; hematopoietic stem cells; hematopoiesis; neutrophils; hematopoietic stem cell; leukocyte count; monkey; colony-forming units assay; intravenous drug administration; colony forming unit gm; tumor necrosis factor; interleukin-1; ape; macaca fascicularis; growth inhibitors; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; bone marrow culture; polymorphonuclear granulocyte count |
| Journal Title: | Blood |
| Volume: | 74 |
| Issue: | 2 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1989-08-01 |
| Start Page: | 547 |
| End Page: | 550 |
| Language: | English |
| PUBMED: | 2787677 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V74.2.547.547 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
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