Circulating Levels of Markers of Inflammation and Endothelial Activation are Increased in Men with Chronic Spinal Cord Injury

Abstract

Accelerated atherogenesis is often seen in individuals with chronic spinal cord injury (SCI). However, the mechanisms contributing to this phenomenon remain unclear. This study aimed to evaluate whether SCI per se is associated with a low-grade chronic inflammatory state and endothelial activation, both of which are well-documented prerequisites for atherogenesis. Methods: Serum levels of markers of inflammation (C-reactive protein [CRP], interleukin-6, and soluble CD40 ligand) and endothelial activation (endothelin-1, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 [sVCAM-1]) were measured in SCI patients with CRP levels < 10 mg/L and with no evidence of active infection. Sixty-two men with traumatic neurologically complete SCI (20 tetraplegics and 42 paraplegics) and 29 age-matched male controls were enrolled. Results: Compared with able-bodied controls, subjects with SCI had a significantly lower body mass index (BMI) (−7%) and significantly lower serum levels of albumin (−10%), creatinine (−20%), low-density lipoprotein cholesterol (−10%), and high-density lipoprotein (HDL) cholesterol (−25%), and showed a trend toward higher fasting insulin levels. Irrespective of injury level and duration, subjects with SCI had significantly higher serum levels, compared to able-bodied controls, of CRP (mean, 4.0 ± 2.7 mg/L vs. 1.4 ± 1.1 mg/L), interleukin-6 (median, 2.5 pg/mL vs. 0.4 pg/mL; range, 1.5–3.6 pg/mL vs. 0.2–0.5 pg/mL), endothelin-1 (mean, 1.3 ± 0.4 pg/mL vs. 0.9 ± 0.3 pg/mL), and sVCAM-1 (mean, 1170 ± 318 ng/mL vs. 542 ± 318 ng/mL). The serum levels of all four factors correlated negatively with levels of serum albumin, creatinine and HDL cholesterol, but not with BMI or fasting insulin levels. In multivariate analyses, SCI was the only factor that was independently associated with increased serum levels of CRP, interleukin-6, endothelin-1 and sVCAM-1 after adjustment for confounding factors such as serum albumin and creatinine levels and parameters of dyslipidemia and insulin resistance. Conclusion: In this study, we have, for the first time, demonstrated that SCI per se is associated with a lowgrade chronic inflammatory state and endothelial activation, which may partly explain the increased atherogenic risk in patients with long-standing SCI.

Keywords

• adhesion molecule
• C-reactive protein
• endothelin
• interleukin-6
• spinal cord injury