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P OSTER
A BSTRACTS
Table 1. Multivariable Odds Ratios (95% Confidence Intervals) for
Malignancy by Serum Ferritin Level
B139
IL-6 inhibits erythroid maturation in human TF-1
erythroleukemia cells.
N. M. Cruz, 1 B. J. McCranor, 1 F. Peña-Cruz, 1 A. E. Berger, 2
C. Cheadle, 2 C. I. Civin, 3 C. N. Roy. 1,4 1. Division of Geriatric
Medicine, Johns Hopkins University School of Medicine, Baltimore,
MD; 2. Lowe Family Genomics Core, Johns Hopkins University
School of Medicine, Baltimore, MD; 3. Center for Stem Cell Biology
& Regenerative Medicine and Departments of Pediatrics and
Physiology, University of Maryland School of Medicine, Baltimore,
MD; 4. Division of Hematology, Johns Hopkins University School of
Medicine, Baltimore, MD.
Supported By: MSTAR/AFAR 5T35AG026758-07; American
Society for Hematology Scholars Award (CNR); R01 DK082722
Background: Approximately 10% percent of adults over 65
years of age are anemic. One-third of cases can be attributed to anemia
of inflammation (AI). Aging, even in the absence of disease, can
be considered a chronic pro-inflammatory state. Interleukin-6 (IL-6)
increases with age and is elevated in the serum of patients with AI.
We tested the hypothesis that IL-6 inhibits erythroid precursor maturation.
To provide rationale for future studies in human volunteers,
we used TF-1 human erythroleukemia cells as an in vitro model of
human erythroid maturation and AI.
Methods: We incubated TF-1 cells overnight in basal medium,
and then treated the cells for 3-4 days with erythropoietin (Epo) to
induce erythroid maturation in the presence or absence of 100 ng/mL
of human IL-6. Erythroid maturation was assessed by staining with
CD44 and glycophorin A (GYPA) monoclonal antibodies and flow
cytometry. We performed quantitative RT-PCR to measure fold
changes in expression of aminolevulinic acid synthase 2 (ALAS2)
and band 3 (SLC4A1), which are markers of heme biosynthesis and
erythroid maturation.
Results: We found that Epo-treated TF-1 cells became phenotypically
more mature, as measured by CD44 and GYPA. The mature
population was 45 ± 11% of total cells, but this population was
reduced to 33 ± 9% of total cells with IL-6 treatment. ALAS2 expression
increased in Epo-treated cells to 10 times that of untreated
cells (p