Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood.

Eda, H., Zhang, J., Keith, R.H., Michener, M., Beidler, D.R., Monahan, J.B.

Journal	Cytokine	Year	2010
Species	Human	Volume	52 (3)
Analytes Measured	Eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1β, IL-10, IL-12 p70, IL-6, IL-8, IP-10, MCP-1, MCP-4, MIP-1β, TARC, TNF-α	Page #	215-220
Matrix Tested	Plasma	Category	Cytokines & Chemokines

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.