Changes in Interleukin-1 alpha serum levels after transplantation of umbilical cord blood cells in a model of perinatal hypoxic-ischemic brain damage

Abstract

Transplantation of human umbilical cord blood (hUCB) cells is a potential approach for the treatment of perinatal hypoxic-ischemic brain injury. Neurological and motor deficits resulting from the brain lesion are ameliorated upon transplantation. The molecular mechanisms underlying these improvements are currently being unravelled. One parameter identified as part of the beneficial effects of hUCB cells is the reduction of brain inflammation. It is, however, unclear whether the modulation of brain inflammation is due to local or systemic effects of hUCB cells. In this study, the effects of hUCB cell transplantation in a model of perinatal hypoxic-ischemic brain injury were investigated at the systemic level by measurement of serum levels of pro-inflammatory cytokines by multiplex bead arrays. Two days after induction of the brain damage, levels of the pro-inflammatory cytokines Interleukin-1α (IL-1α), Interleukin-1β (IL-1β), and Tumor necrosis factor α (TNFα) were increased in the serum of rats. Application of hUCB cells, in turn, correlated with a reduced elevation of serum levels of these pro-inflammatory cytokines. This decrease was accompanied by a reduced expression of CD68, a marker protein of activated microglia/macrophages in the brain. Therefore, systemic modulation of the immune response by hUCB cells could represent one possible mechanism of how these cells might mediate their beneficial effects. Creation of a regenerative environment with reduced inflammation might account for the functional regeneration observed upon hUCB cell treatment in lesioned animals.