Serial changes of cytokines in children with cerebral palsy who received intravenous G-CSF followed by autologous mobilized peripheral blood mononuclear cells

Abstract

Purpose: This study was performed to assess serial cytokine changes and their clinical impact in children with cerebral palsy (CP) who participated in a clinical trial of granulocyte-colony stimulating factor (G-CSF) followed by infusion of autologous mobilized peripheral blood mononuclear cells (mPBMCs). Methods: Peripheral blood (PB) samples were collected from 16 CP children at enrollment (M0), and 1 month (M1) and 7 months (M7) after G-CSF infusion before collecting and infusing autologous mPBMCs or placebo, as well as at the end of the study (M13). Plasma samples were stored at -80°C until the end of the experiment. Levels of G-CSF, brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin like growth factor (IGF)-1, interleukin (IL)-6, IL-8, and IL-10 were measured by enzyme-linked immunosorbent assays with plasma samples. Clinical responses were assessed by a rehabilitation medicine specialist according to scores in various evaluation tools. Results: G-CSF levels were significantly elevated at M1 and decreased to baseline by M7. VEGF, IL-6, and IL-10 behaved in the same way whereas BDNF and IGF-1 followed the reverse pattern, falling initially and then returning to baseline. There were no significant differences in cytokine levels between the mPBMC and placebo groups over 6 months. However, when clinical responders and non-responders were compared, IL-6 (p=0.05) as well as G-CSF (p=0.001) were higher in the responders than the non-responders at M1, while BDNF (p=0.03) and IGF-1 (p=0.001) were lower. In addition, BDNF was higher at baseline in the responders than the non-responders (p=0.03). Conclusion: The changes of G-CSF itself, as well as G-CSF-induced cytokines such as IL-6, may be associated with the clinical improvement of neurologic functions. The G-CSF-induced changes of IL-6, BDNF and IGF-1, and BDNF levels before treatment, could be used as prognostic factors in G-CSF trials in CP children.