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Updated: Jun 9, 2026
Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood
Hiroyuki Eda1, Jian Zhang, Robert H Keith
1Discovery Biology, Global Research and Development, St. Louis Laboratories, Pfizer Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA. hiroyuki_eda@ajinomoto.com
Insights
Macrophage-colony stimulating factor (M-CSF) and interleukin-34 (IL-34) induce chemokines, particularly MCP-1, in human whole blood. This response is inhibited by M-CSF receptor and c-FMS kinase inhibitors, suggesting MCP-1 assays are valuable for drug development.
Area of Science:
- Immunology
- Pharmacology
Background:
- Macrophage-colony stimulating factor (M-CSF) and interleukin-34 (IL-34) are key regulators of myeloid cell function.
- Understanding their downstream effects on cytokine and chemokine production is crucial for therapeutic targeting.
Purpose of the Study:
- To investigate M-CSF and IL-34's ability to induce cytokines/chemokines in human whole blood (HWB).
- To determine if soluble M-CSF receptor or c-FMS kinase inhibitors can block M-CSF/IL-34-induced responses.
- To identify optimal chemokine targets for evaluating c-FMS kinase inhibitor potency.
Main Methods:
- Incubation of HWB with M-CSF or IL-34.
- Measurement of cytokine (IL-6) and chemokine (IP-10, IL-8, MCP-1) levels.
- Inhibition assays using soluble M-CSF receptor and a c-FMS kinase inhibitor (GW2580).
Main Results:
- M-CSF and IL-34 significantly increased IL-6 and chemokine levels (IP-10, IL-8, MCP-1) in HWB, with MCP-1 showing less donor variability.
- Soluble M-CSF receptor reduced chemokine elevation, confirming M-CSF/IL-34 mediation.
- GW2580 inhibited MCP-1 induction in a dose-dependent manner.
Conclusions:
- MCP-1 is the most suitable chemokine for assays evaluating c-FMS kinase inhibitors.
- A human whole blood MCP-1 release assay is a relevant tool for the translational pharmacology of c-FMS kinase inhibitors.
Abstract:
The aim of this study is to investigate if macrophage-colony stimulating factor (M-CSF) or interleukin-34 (IL-34) induces cytokines or chemokines using human whole blood (HWB) and if an M-CSF- or IL-34-induced cytokine or chemokine production from HWB is inhibited by soluble M-CSF receptor or c-FMS kinase inhibitors. Among eight cytokines or growth factors tested, only IL-6 level was increased by up to 6-fold by M-CSF or IL-34 in HWB. In contrast, chemokine levels (IP-10/CXCL10, IL-8/CXCL8, and MCP-1/CCL2) were dramatically increased by M-CSF or IL-34 in HWB while exhibiting a large variation among donors. Variability of the MCP-1 signal induced by M-CSF or IL-34 was relatively less among donors compared to the IP-10 and IL-8 signals. The elevation of these chemokine levels was significantly decreased by soluble M-CSF receptor, indicating the elevation of these chemokines was mediated by M-CSF or IL-34. Furthermore, GW2580, a c-FMS kinase inhibitor, inhibited the induction of MCP-1 by M-CSF or IL-34 in a concentration dependent manner. These indicate MCP-1 is the most appropriate chemokine target for a chemokine release assay to evaluate the potency of c-FMS kinase inhibitors and MCP-1 release assay using HWB would be useful, relevant tool for translational pharmacology of c-FMS kinase inhibitors.
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