IL-6 Mobilizes Bone Marrow-Derived Cells to the Vascular Wall, Resulting in Neointima Formation via Inflammatory Effects

Aim: Among the many factors related to bone marrow cell mobilization, local inflammation induced by cytokines may drive bone marrow cells to the vascular wall, resulting in a thickened neointima. However, the relationship between inflammatory reactions and bone marrow cell invasion has not yet been fully clarified. Methods: We inserted a large wire into the femoral artery in male balb/c(WT), interleukin (IL)-6-knockout(KO) and bone marrow-transplanted(BMT) mice that had received bone marrow cells from KO mice. Immunohistochemistry was performed to evaluate the degree of intimal hyperplasia and inflammation following vascular injury. Results: Three days after the vascular injury, the number of CD34/Sca-1-positive cells in the blood was higher in the KO mice. The numbers of apoptotic cells in the neointima was lower in the KO and BMT mice at two hours after injury. The morphometric analysis performed at one and four weeks after injury showed that the intima/media ratio was significantly lower in the KO and BMT mice, while CD34-positive cells were much more frequent in the WT mice. Furthermore, re-endothelialization appeared earlier in the KO and BMT mice than in the WT mice. No differences in the levels of vascular endothelial growth factor or hepatocyte growth factor were observed in the mice sera between the WT, KO and BMT mice after injury. The in vitro culture of bone marrow cells showed more differentiated smooth muscle-like cells in the WT mice than in the KO mice. Conclusions: IL-6 is involved in neointimal formation following vascular injury, possibly acting through inflammatory effects inducing the production of bone marrow cells.