IKK-β-mediated myeloid cell activation exacerbates inflammation and inhibits recovery after spinal cord injury

Traumatic spinal cord injury (SCI) is followed by massive infiltration and activation of myeloid cells such as neutrophils and macrophages, but the functions of these cells are controversial. In this study, our objective was to elucidate the in vivo role of a signaling pathway involved in activation of these innate immune cells in SCI using myeloid cell-specific I kappa B kinase (IKK)-beta conditional knockout (ikkb beta(Delta mye)) mice. In these mice, the ikk beta gene has been specifically deleted from myeloid cells, compromising their in vivo IKK/NF-kappa B-dependent activation. We found that ikk beta(Delta mye) mice had significantly reduced neutrophil and macrophage infiltrations after SCI compared to ikk beta(+/+) controls. SCI-induced proinflammatory gene expression was also reduced in ikk beta(Delta mye) mice. Reduced neuroinflammation in ikk beta(Delta mye) mice was accompanied by attenuated neuronal loss and behavioral deficits in motor activity. In addition, the SCI-induced expression of CXC ligand 1 was reduced in ikk beta(Delta mye) mice, which may be responsible for the reduced neutrophil infiltration in these mice. Our data demonstrate that IKK-beta-dependent myeloid cell activation potentiates neuroinflammation and neuronal damage after SCI.