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


METHODS
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, -1beta, -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 TNFalpha peaked at 5 minutes after declamping, but decreased afterwards. Plasma TNFalpha 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 TNFalpha 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.
Kunihara
T
T
Department of Cardiovascular Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Sasaki
S
S
Shiiya
N
N
Ishikura
H
H
Kawarada
Y
Y
Matsukawa
A
A
Yasuda
K
K
D000818:Animals; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8 / Q000096:biosynthesis*; D007511:Ischemia / Q000150:complications; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D013119:Spinal Cord Injuries / Q000209:etiology / Q000378:metabolism*
D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D018696:Neuroprotective Agents; D011281:Pregnatrienes; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; C074965:U 74389F