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Ann Thorac Surg 2000;69:792-798
© 2000 The Society of Thoracic Surgeons

Original Articles

Lazaroid reduces production of IL-8 and IL-1 receptor antagonist in ischemic spinal cord injury

Takashi Kunihara, MDa, Shigeyuki Sasaki, MDa, Norihiko Shiiya, MDa, Hiroshi Ishikura, MDb, Yo Kawarada, MDb, Akihiro Matsukawa, MDa,b, Keishu Yasuda, MDa

a Department of Cardiovascular Surgery, Hokkaido University School of Medicine, Sapporo, Japan
b First Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan

Address reprint requests to Dr Sasaki, Department of Cardiovascular Surgery, Hokkaido University Hospital, N-14, W-5, Kita-ku, Sapporo, Japan 0608648
e-mail: sasakish{at}med.hokudai.ac.jp

Background. 21-aminosteroids (lazaroids) have demonstrated the protective effect against cerebral ischemic injury through the inhibition of lipid peroxidation. We examined whether lazaroids affected the production of proinflammatory and antiinflammatory cytokines in ischemic spinal cord injury model.

Materials. Anesthetized New Zealand white rabbits underwent a 20-minute infrarenal aortic cross-clamping (AXC) with pretreatment of either an intravenous 3 mg/kg lazaroid U74389G (group L; n = 10) or the same volume saline (group P; n = 10). Sham operation group (group S; n = 6) underwent only exposure of the aorta. Plasma concentrations of interleukin (IL)-8, -1ß, -1 receptor antagonist (IL-1ra) and tumor necrosis factor (TNF)-{alpha} were measured at four time points. Functional assessment with Tarlov score at 24 and 48 hours after pretreatment, pathologic assessment of the spinal cord, and measurements of cytokine levels in the spinal cord were performed.

Results. The maximum elevation of plasma IL-8 and -1ra levels occurred at 1 hour after declamping in four measurement points. Plasma IL-8 and -1ra levels in group L were significantly lower than those in group P (*p < 0.05). Plasma TNF{alpha} peaked at 5 minutes after declamping, but decreased afterwards. Plasma TNF{alpha} levels were not different among three groups. Spinal IL-8 levels in group L (0.98 ± 0.34 ng/g tissue) were lower than those in group P (7.26 ± 2.26 ng/g tissue)(*p < 0.05). Spinal IL-1ra and TNF{alpha} were not significantly different. Tarlov score and pathologic assessment were better in group L.

Conclusions. Lazaroid U-74389G reduced the production of systemic IL-8 and -1ra and spinal IL-8 when AXC caused spinal cord injury. These results indicate that lazaroids may attenuate ischemic endothelial cell injury or activation of leukocytes.






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