[Effects of specific removal of circulating tumor necrosis factor-alpha by immunoadsorption on nitric oxide in endotoxin shock].

OBJECTIVES

To evaluate the effects of specific removal of circulating TNF-alpha by immunoadsorption on nitric oxide (NO) in endotoxin shock.

METHODS

Immunoadsorbent against TNF-alpha was produced by the attachment of anti-TNF-alpha monoclonal antibody (McAb) to agarose beads. Blank columns were made of agarose beads without the attachment of anti-TNF-alpha McAb. New Zealand white rabbits were injected intravenously with Lipopolysaccharide (LPS, Escherichia coli O111: B4, 8.0 x 10(9) cfu/kg. B.W), and then were randomly divided into three groups: (1) control group(n = 25); without other treatment. (2) pseudoperfusion group(n = 25): rabbits underwent hemoperfusion through the blank columns. (3) perfusion group (n = 15): rabbits underwent hemoperfusion through the immunoadsorbent columns. Hemoperfusion was started at 1 h after the injection of LPS, and was sustained for two hours with blood flow rate of 5 ml/min.

RESULTS

Mean arterial pressure in the perfusion group was significantly increased at 30 min after hemoperfusion (P < 0.05). It maintained a level higher than that before hemoperfusion (P < 0.05), and was higher (P < 0.05) than that in the control and pseudoperfusion groups at 3 h (end of the monitoring period). The plasma TNF-alpha level in the perfusion group was significantly lower than that in the other two groups at 2, 3 and 6 hour after LPS injection (P < 0.05). Although the concentration of plasma nitrite (NO2-, one of the stable end products of NO) in the perfusion group was significantly lower (P < 0.05) than that in the other two groups from 3 h after LPS infusion, it was significantly higher (P < 0.05) than the baseline value from 30 min to 12 h. The activities of NO synthase (NOS) in the heart and lung were significantly lower (P < 0.05) in the perfusion group than in the other two groups at 24 h. The serum levels of alanine transaminase, aspartate transaminase, urea nitrogen, creatinine, lactate dehydrogenase, alpha-hydrobulyric dehydrogenase and alkaline phosphatase in the perfusion group were significantly lower (P < 0.05) than those in the other two groups at 24 h. Moreover, the survival rate of rabbits in the perfusion group was higher (P < 0.05) than that of the other two groups at 24 h.

CONCLUSION

Specific removal of circulating TNF-alpha by immunoadsorption actually acts as the selective inhibition of the inducible NOS(iNOS) and may be a new and effective therapy for endotoxin shock.