Administration of hematopoietic cytokines increases the expression of anti-inflammatory cytokine (IL-10) mRNA in the subacute phase after stroke

We investigated the effect of the subcutaneous administration of hematopoietic cytokines, granulocyte colony-stimulating factor (G-CSF) + stem cell factor (SCF), on mRNA expression of tissue cytokines in the acute or subacute phase after focal ischemia in male C57 BL/6J mice. The expression of IL-10 mRNA was elevated at 4–14 days after occlusion when cytokines were given in the acute phase (days 1–10). The expression of IL-10 mRNA was markedly elevated at 14 days after occlusion, then remained high until 28 days when cytokines were given in the subacute phase (days 11–20). However, there were no significant changes in IL-6, TGF-β1, TNF, G-CSF, SCF and iNOS expression following either acute- or subacute-phase treatment. Further, hematopoietic cytokine treatment in the subacute phase, but not in the acute phase, reduced ED1-positive microglia/macrophages in the infarcted brain. Our recent study showed that the subacute-phase treatment is effective for functional recovery, enhancing generation of neuronal cells from both bone-marrow-derived and neural stem/progenitor cells. Taken together, these results suggest that cytokine treatment in the subacute phase may provide a favorable microenvironment for neurogenesis after ischemic stroke through the up-regulation of IL-10.