Traumatic injury can cause a systemic inflammatory response, increasing oxidative activity of circulating leukocytes and potentially exacerbating the original injury, as well as causing damage to initially unaffected organs. Although the importance of intraspinal
inflammation after human
spinal cord injury is appreciated, the role of the systemic inflammatory response to this injury is not widely recognised. We investigated oxidative activity of blood leukocytes from nine cord-injured subjects and six
trauma controls (
bone fractures without CNS injury) at 6 h-2 weeks after injury, comparing values to those of ten uninjured subjects. Neutrophil and monocyte
free radical production, evaluated by flow cytometry, increased significantly more in cord injury subjects than in
trauma controls (6-fold vs 50% increases). In leukocyte homogenates, the concentration of
free radicals increased significantly more in cord injury subjects (2-fold) than in the
trauma controls (1.6-fold) as did activity of
myeloperoxidase (2.3-fold vs. 1.7-fold). Moreover, in homogenates and blood smears, expression of the
NADPH oxidase subunit gp91(
phox) and of the oxidative
enzyme, inducible
nitric oxide synthetase was 20-25% greater in cord injury subjects than in
trauma controls. Expression of the pro-inflammatory
transcription factor NF-kappaB and of
cyclooxygenase-2 increased similarly after both
injuries. Finally,
aldehyde products of tissue-damaging lipid peroxidation also increased significantly more in the plasma of
spinal cord injury subjects than in
trauma controls (2.6 fold vs. 1.9-fold).
Spinal cord injury causes a particularly intense systemic inflammatory response. Limiting this response briefly after cord injury should protect the spinal cord and tissues/organs outside the CNS from secondary damage.