[The effects of removing circulated TNF by immunoadsorption on renal changes in rabbits with endotoxin shock]

To remove circulating tumor necrosis factor (TNF) by specific immunoadsorption column containing anti-TNF monoclonal antibody (McAb) and observe the effects of the therapy on renal changes in experimental endotoxin shock.

New Zealand white rabbits were injected with lethal dose of E. coli endotoxin (LPS, 8 x 10(9) cfu/kg) to produce endotoxin shock, then were divided into two groups: control (n = 7) and perfusion group (n = 10). Perfusion was started at 1 hour after administration of endotoxin. Mean arterial pressure (MAP) was monitored continuously. Blood samples were collected for assay of TNF, urea nitrogen (BUN) and creation (Cr). Six hours after infusion of LPS, rabbits were sacrificed, then the kidney was taken for pathologic observation.

MAP was increased 30 minutes after perfusion in perfusion group, then kept at a level higher than that in the control group in the monitoring period (P < 0.01). The plasma TNF activation was reduced significantly in the perfusion group (44 +/- 10) compared with the control group (1448 +/- 226, P < 0.05) one hour after perfusion. The levels of BUN and Cr were decreased in the perfusion group compared with the control group. The degree of glomerular congestion and infiltration of leukocytes in glomeruli was significantly lower in the perfusion group than in the control group. The degree of tubular necrosis was decreased significantly in the perfusion group compared to that in the control group (P < 0.05). The mitochondrial ultrastructural changes were more severe in the control group than in the perfusion group.

Specific immunoadsorptive column containing anti-TNFMcAb could remove effectively circulating TNF in experimental endotoxin shock. Reducing levels of TNF in the early phase of endotoxin shock may ameliorate the state of hypotension.