Interleukin-6 is a major effector molecule of short-term G-CSF treatment inducing bone metabolism and an acute-phase response

Objective The biological steps leading to hematopoietic progenitor cell (HPC) mobilization from the bone marrow to the peripheral blood compartment during G-CSF treatment are still poorly defined. In this study, we investigated G-CSF–mediated secretion of cytokines as potential mediators. Materials and Methods Plasma and urine samples from G-CSF–mobilized donors for HPC transplantation were collected before and during mobilization therapy. Interleukin-6 (IL-6), alkaline phosphatase (ALP), bone-specific ALP (bone ALP), C-reactive protein (CRP), lipopolysaccharide binding protein (LPB), CD34+ cells and urinary deoxypyridinoline (DPD) concentrations were measured and statistically correlated. Results IL-6 was highly elevated at days 4 and 5 of G-CSF treatment. G-CSF administration led to elevation of IL-6 parallel to the appearance of CD34+ cells in the peripheral blood. Major metabolic changes such as high bone ALP plasma concentration and urinary excretion of deoxypyridinoline (DPD), indicating stimulation of bone metabolism, were observed. Elevated concentrations of CRP and LPB indicated an acute-phase response. Furthermore, CRP concentrations correlated significantly with the percentage of mobilized CD34+ cells. Conclusion Based on these findings, we propose IL-6 as a major physiological effector molecule of G-CSF treatment that induces bone metabolism and an acute-phase reaction along with mobilization of CD34+ cells in the peripheral blood. IL-6 may be responsible for osteopenia observed during short- and long-term G-CSF treatment. These observations may also have implications for G-CSF treatment of patients with plasmocytoma.