Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)alpha is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNF alpha, interleukin (IL)-1 beta, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naive controls. mRNA levels of the proinflammatory cytokines IL-1 beta, IL-6, TNF alpha, and C-fos, and TNF alpha and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFac remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNF alpha levels were sustained in the kidney only after T10 SCI. TNF alpha protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.