PMID- 9708448
OWN - NLM
STAT- MEDLINE
DCOM- 19981104
LR  - 20131121
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 16
IP  - 4
DP  - 1998
TI  - Effects of myelotoxic agents on cytokine production in murine long-term bone 
      marrow cultures.
PG  - 261-70
AB  - In long-term bone marrow cultures we studied the effect of the addition of the 
      myelotoxic agents methotrexate (MTX) and ceftazidime (CEF) on the kinetics of 
      cytokine production in the supernatant (SN) and on mRNA expression in the 
      adherent stromal layer. In response to a medium change, a prompt and significant 
      increase in colony-stimulating activity (CSA) and interleukin 6 (IL-6) 
      concentrations in the SN occurred, peaking 12 h later. Two macrophage 
      colony-stimulating factors (M-CSF) mRNA of 23 kb and 4 kb were identified. In 
      response to the medium change, the 4.0-kb transcript increased significantly six 
      h later. The 2.3-kb transcript expression was stronger than the 4-kb mRNA but did 
      not cycle with medium change. At medium change, IL-6 mRNA was only minimally 
      expressed; then a prompt increase occurred, which peaked six h later. The 
      addition of 500 mg/ml (=915 microM) CEF to the culture caused a dose-dependent 
      suppression of CSA and IL-6 supernatant concentrations and IL-6 and M-CSF mRNA 
      expression. By contrast, 1 microM MTX had minimal effect on cytokine 
      concentrations in the SN following medium change. mRNA expression was, however, 
      suppressed. These results provide insights into the possible mechanisms whereby 
      cytokines lead to increased myeloid cell proliferation following medium change. 
      We also demonstrate that two myelotoxic agents have different effects on cytokine 
      production. This information could be of value in developing rational approaches 
      to the therapeutic use of cytokines in drug-induced neutropenia.
FAU - Hauser, S P
AU  - Hauser SP
AD  - Department of Medicine, University of Arkansas for Medical Sciences, and 
      Geriatric Research, Education and Clinical Center, John L. McClellan Memorial 
      Veterans Administration Hospital, Little Rock, USA.
FAU - Allewelt, M C
AU  - Allewelt MC
FAU - Lipschitz, D A
AU  - Lipschitz DA
LA  - eng
GR  - AG 07473/AG/NIA NIH HHS/United States
GR  - AG 09458/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Growth Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Messenger)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 9M416Z9QNR (Ceftazidime)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*drug effects/metabolism
MH  - Ceftazidime/*pharmacology
MH  - Cell Culture Techniques
MH  - Female
MH  - Gene Expression
MH  - Growth Inhibitors/*pharmacology
MH  - Interleukin-6/*biosynthesis/genetics
MH  - Macrophage Colony-Stimulating Factor/*biosynthesis/genetics
MH  - Methotrexate/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RNA, Messenger
MH  - Time Factors
EDAT- 1998/08/26 00:00
MHDA- 1998/08/26 00:01
CRDT- 1998/08/26 00:00
PHST- 1998/08/26 00:00 [pubmed]
PHST- 1998/08/26 00:01 [medline]
PHST- 1998/08/26 00:00 [entrez]
AID - 10.1002/stem.160261 [doi]
PST - ppublish
SO  - Stem Cells. 1998;16(4):261-70. doi: 10.1002/stem.160261.