Serial Changes of Cytokines in Children with Cerebral Palsy Who Received Intravenous Granulocyte-colony Stimulating Factor Followed by Autologous Mobilized Peripheral Blood Mononuclear Cells

Abstract

Background: This study was performed to assess serial cytokine changes and their clinical impact in children with cerebral palsy (CP) who received 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, and 1 month and 7 months after G-CSF infusion as well as at the end of the study. Cytokine levels were measured by enzyme-linked immunosorbent assays with plasma samples.

Results: 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, interleukin (IL)-6 (P = 0.050) as well as G-CSF (P = 0.010) were higher in the responders than the non-responders at 1 month, while brain-derived neurotrophic factor (BDNF) (P = 0.030) and insulin-like growth factor (IGF)-1 (P = 0.001) were lower. In addition, BDNF was higher at baseline in the responders than the non-responders (P = 0.030).

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.