Early expression and cellular localization of proinflammatory cytokines interleukin-1[beta], interleukin-6, and tumor necrosis factor-[alpha] in human traumatic spinal cord injury

Abstract

Study Design. Post-traumatic inflammatory response was studied in 11 human cases of acute spinal cord contusion injury. Objectives. To examine the inflammatory cellular response and the immunocytochemical expression and localization of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha]in human spinal cord after contusion injury. Summary of Background Data. The post-traumatic inflammatory response plays an important role in secondary injury mechanisms after spinal cord injury, and inter-leukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha] are key inflammatory mediators. Methods. The study group comprised 11 patients with spinal cord contusion injury and 2 normal individuals. Histologic and immunocytochemical assessments were undertaken to evaluate the inflammatory cellular response and the immunoexpression of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha] in the injured human spinal cord. The cellular sources of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha] were elucidated by immunofluorescence double-labeled confocal imaging. Results. Increased immunoreactivity of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha]was detected in neurons 0.5 hour after injury, and in neurons and microglia 5 hours after injury, but the expression of these proinflammatory cytokines was short-lived and declined sharply to baseline by 2 days after injury. In the inflammatory cellular response, as early as 0.5 hour after spinal cord injury, activated microglia were detected, and axonal swellings and axons were surrounded by microglial processes. Numerous neutrophils appeared in the injured cord 1 day after injury, and then their number declined dramatically, whereas macrophages progressively increased after day 1. Conclusions: Endogenous cells (neurons and microglia) in the human spinal cord, not the blood-borne leukocytes, contribute to the early production of interleukin-1[beta], interleukin-6, and tumor necrosis factor-[alpha] in the post-traumatic inflammatory response, and microglia are involved the early response to traumatic axonal injury.