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-beta1, 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.