Cytokine effects on erythroid proliferation and hemoglobin modulation
| Cytokine (concentration) . | EPO . | EPO + cytokine . | ||
|---|---|---|---|---|
| Cell count, ×106 . | HbF/HbA, % . | Cell count, ×106 (P) . | HbF/HbA, % (P) . | |
| SCF (50 ng/mL) | 0.60 ± 0.40 | 2.5 ± 0.68 | 2.65 ± 0.40 (.02) | 21 ± 1.4 (.0004) |
| IL-6 (200 ng/mL) | 0.53 ± 0.15 | 5.1 ± 1.7 | 1.8 ± 2.0 (.20) | 8.7 ± 2.9 (.05) |
| LIF (500 ng/mL) | 0.28 ± 0.1 | 6.3 ± 3.6 | 0.28 ± 0.11 (.46) | 6.1 ± 3.4 (.40) |
| Activin (100 ng/mL) | 0.33 ± 0.17 | 4.8 ± 3.1 | 0.22 ± 0.11 (.05) | 5.7 ± 2.2 (.31) |
| IGF-II (50 ng/mL) | 0.22 ± 0.10 | 7 ± 1.41 | 0.45 ± 0.20 (.24) | 5.5 ± 2.1 (.31) |
| BMP 4 (1 μg/mL) | 0.26 ± 0.11 | 3.2 ± 5.3 | 0.25 ± 0.24 (.48) | 3.9 ± 5.0 (.18) |
| IL-3 (10 ng/mL) | 0.63 ± 0.22 | 3.9 ± 1.7 | 3.5 ± 0.95 (.0003) | 4.6 ± 1.4 (.14) |
| GM-CSF (10 ng/mL) | 0.63 ± 0.22 | 3.1 ± 1.7 | 2.0 ± 1.5 (.02) | 3.9 ± 1.3 (.50) |
| bFGF (200 ng/mL) | 0.29 ± 0.02 | 4.0 ± 3.4 | 0.28 ± 0.01 (.29) | 3.9 ± 3.1 (.35) |
| HGF (100 ng/mL) | 0.72 ± 0.52 | 2.5 ± 2.3 | 0.73 ± 0.53 (.34) | 3.7 ± 2.9 (.12) |
| IGF-I (50 ng/mL) | 0.19 ± 0.07 | 4.2 ± 2.6 | 0.83 ± 0.66 (.33) | 3.5 ± 0.78 (.33) |
| OSM (200 ng/mL) | 0.49 ± 0.30 | 4.1 ± 2.8 | 1.5 ± 1.7 (.23) | 3.2 ± 1.1 (.30) |
| Cytokine (concentration) . | EPO . | EPO + cytokine . | ||
|---|---|---|---|---|
| Cell count, ×106 . | HbF/HbA, % . | Cell count, ×106 (P) . | HbF/HbA, % (P) . | |
| SCF (50 ng/mL) | 0.60 ± 0.40 | 2.5 ± 0.68 | 2.65 ± 0.40 (.02) | 21 ± 1.4 (.0004) |
| IL-6 (200 ng/mL) | 0.53 ± 0.15 | 5.1 ± 1.7 | 1.8 ± 2.0 (.20) | 8.7 ± 2.9 (.05) |
| LIF (500 ng/mL) | 0.28 ± 0.1 | 6.3 ± 3.6 | 0.28 ± 0.11 (.46) | 6.1 ± 3.4 (.40) |
| Activin (100 ng/mL) | 0.33 ± 0.17 | 4.8 ± 3.1 | 0.22 ± 0.11 (.05) | 5.7 ± 2.2 (.31) |
| IGF-II (50 ng/mL) | 0.22 ± 0.10 | 7 ± 1.41 | 0.45 ± 0.20 (.24) | 5.5 ± 2.1 (.31) |
| BMP 4 (1 μg/mL) | 0.26 ± 0.11 | 3.2 ± 5.3 | 0.25 ± 0.24 (.48) | 3.9 ± 5.0 (.18) |
| IL-3 (10 ng/mL) | 0.63 ± 0.22 | 3.9 ± 1.7 | 3.5 ± 0.95 (.0003) | 4.6 ± 1.4 (.14) |
| GM-CSF (10 ng/mL) | 0.63 ± 0.22 | 3.1 ± 1.7 | 2.0 ± 1.5 (.02) | 3.9 ± 1.3 (.50) |
| bFGF (200 ng/mL) | 0.29 ± 0.02 | 4.0 ± 3.4 | 0.28 ± 0.01 (.29) | 3.9 ± 3.1 (.35) |
| HGF (100 ng/mL) | 0.72 ± 0.52 | 2.5 ± 2.3 | 0.73 ± 0.53 (.34) | 3.7 ± 2.9 (.12) |
| IGF-I (50 ng/mL) | 0.19 ± 0.07 | 4.2 ± 2.6 | 0.83 ± 0.66 (.33) | 3.5 ± 0.78 (.33) |
| OSM (200 ng/mL) | 0.49 ± 0.30 | 4.1 ± 2.8 | 1.5 ± 1.7 (.23) | 3.2 ± 1.1 (.30) |
Erythroid progenitors from the buffy coats of blood donations were cultured for 2 weeks in matched pairs, in the presence of 4 U/mL erythropoietin alone (EPO) or EPO plus an additional cytokine as indicated. Cell counts per milliliter culture medium and HbF/HbA ratios expressed as percentages are shown with SDs. Cells collected from 35 blood donations were cultured separately for duplicate or triplicate analysis of each cytokine. Two-tailed, pairedt test analyses were preformed to determine the significance of the cytokines. The cytokines are listed in descending order according to their effect on the HbF/HbA ratio.
LIF indicates leukemia inhibitory factor; activin, activin A; IGF-II, insulinlike growth factor II; BMP 4, bone morphogenetic protein 4; HGF, hepatocyte growth factor; IGF-I, insulinlike growth factor I; and OSM, oncostatin M.