ALTERATIONS OF BACTERIAL CLEARANCE INDUCED BY ENDOTOXIN AND TUMOR-NECROSIS-FACTOR

The purpose of the study was to investigate the potential influence of endotoxin and tumor necrosis factor (TNF) on immune function in terms of systemic clearance and organ distribution of injected Escherichia coli in a rabbit model. To enable quantification of the clearance proc ess, defined numbers of exogenous E. coli (1.3 X 10(8) CFU) were injec ted intravenously 60 min after bolus application of TNF (4 X 10(5) U, n = 6), after infusion of endotoxin (40 mug/kg of body weight) for 1 h (n = 6) or 4 h (n = 6), or after saline infusion (controls, n = 6). P arameters monitored were arterial pressure, oxygen uptake, and rates o f bacterial elimination from the blood. At 180 min after E. coli injec tion, the animals were sacrificed, and tissue samples of liver, kidney , spleen, and lung were collected for bacterial counts. Endotoxin infu sion produced a significant delay in blood clearance compared with sal ine and TNF pretreatment. The diminished systemic bacterial eliminatio n was associated with significantly higher numbers of E. coli in the o rgans, thus reflecting reticuloendothelial system dysfunction. TNF had no major influence on the elimination kinetics of bacteria but affect ed the tissue distribution pattern with increased accumulation of E. c oli in the lung (up to 100-fold of control values; P < 0.001).