Effect of anti-rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthase expression, sodium- and potassium-activated, magnesium-dependent adenosine-5 '-triphosphatase and superoxide dismutase activation, and ultrastructural changes

1st Interdisciplinary World Congress on Spinal Surgery -- AUG 27-SEP 01, 2000 -- BERLIN, GERMANYWOS: 000169688300011PubMed ID: 11453434Object. The inflammatory cells that accumulate at the damaged site after spinal cord injury (SCI) may secrete interleukin-6 (IL-6), a mediator known to induce the expression of inducible nitric oxide synthase (iNOS). Any increased production of NO by iNOS activity would aggravate the primary neurological damage in SCI. If this mechanism does occur, the direct or indirect effects of IL-6 antagonists on iNOS activity should modulate this secondary injury. In this study, the authors produced spinal cord damage in rats and applied anti-rat IL-6 antibody to neutralize IL-6 bioactivity and to reduce iNOS. They determined the spinal cord tissue activities of Na+-K+/Mg++ adenosine-5 ' -triphosphatase (ATPase) and superoxide dismutase, evaluated iNOS immunoreactivity, and examined ultrastructural findings to assess the results of this treatment. Methods. Seventy rats were randomly allocated to four groups. Group I (10 rats) were killed to provide normal spinal cord tissue for testing. In Group II 20 rats underwent six-level laminectomy for the effects of total laminectomy alone to be determined. In Group III 20 rats underwent six-level T2-7 laminectomy and SCI was produced by extradural compression of the exposed cord. The same procedures were performed in the 20 Group TV rats, but these rats also received one (2 mug) intraperitoneal injection of anti-rat IL-6 antibody immediately after the injury and a second dose 24 hours posttrauma. Half of the rats from each of Groups II through TV were killed at 2 hours and the other half at 48 hours posttrauma. The exposed cord segments were immediately removed and processed for analysis. Conclusions. The results showed that neutralizing IL-6 bioactivity with anti-rat IL-6 antibody significantly attenuates iNOS activity and reduces secondary structural changes in damaged rat spinal cord tissue