The Expression of Inflammatory Cytokines Following Acute Spinal Cord Injury: A Human versus Animal Model Comparison

Introduction: Inflammation is an important pathophysiologic process in the secondary injury cascade following spinal cord injury (SCI), and many neuroprotective strategies (eg. methylprednisolone) attempt to attenuate its damaging effects. Virtually everything known about post-SCI inflammation and the cytokines that mediate it has been obtained from animal models. However, it is not known how closely inflammation in these rat models represents the human condition. The purpose of this study was to evaluate the expression of inflammatory cytokines within the cerebrospinal fluid (CSF) of patients with acute SCI, and to compare this expression to that observed in a well established animal model.

Methods: A lumbar intrathecal catheter was installed into 10 adult patients with acute SCI, and CSF samples were obtained at regular intervals for 3-7 days. In parallel investigations, Sprague Dawley rats underwent a thoracic cord contusion using the Ohio State University Impactor, and the CSF and spinal cords were extracted at similar time points. The human and rat tissues were evaluated with a BioPlex Protein Array system to assess such cytokines as IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, and TNF-alpha.

Results: Many inflammatory cytokines were similarly elevated in human and rat samples within 24 hours of injury, including IL-1beta, IL-2, IL-4, IL-10, TNF-alpha, and IFN-gamma. Most cytokine levels diminished by 72 hours after injury. The levels of all inflammatory cytokines in non-injured control patients (hip and knee replacement patients undergoing spinal anesthetics) were either low or too low to be measured.

Conclusion: This study represents the first description of the temporal sequence of inflammatory cytokine expression in human CSF after spinal cord injury. It provides valuable insight into the similarities and differences between human SCI and the rat model that attempts to simulate it Such translational research studies help to target basic science research in clinically relevant directions.

Hibbs Award Nominee for Best Basic Science Paper