Tolerance to Bacterial Endotoxin Produced by Proliferation of Gram Negative Bacteria in the Kidney

Tolerance to the toxic effects of endotoxins of Gram negative bacteria has been demonstrated only after repeated injections of dead Gram negative bacteria or their products, but not during the course of clinical or experimental infections 1 , 2 , 3 . Previous clinical observations by the author suggested that tolerance to bacterial endotoxin did occur during the course of human pyelonephritis and prompted investigation of the effect of experimental pyelonephritis on the pyrogenic response to endotoxins. This preliminary report is based upon the initial observations made during this study. Material and methods. Unilateral pyelonephritis was produced in six 2.0-3.0 kg male New Zealand rabbits by intravenous injection of 1 × 109 E. coli (0-111:B-4), followed immediately by occlusion of the right ureter for 36 hours. A loose ligature had been placed about the ureter previously through a right flank surgical approach and fixed externally for subsequent tightening. Six weight matched control rabbits underwent a similar operative procedure without ureteral occlusion and received an equivalent endotoxin challenge of 1 × 109 formalin killed E. coli (0-111:B-4) on the same day. The pyrogenic response of the control and pyelonephritic rabbits to 0.5 μg of purified S. enteriditis lipopolysaccharide (Difco) was determined 10 to 21 days later. The rabbits were maintained in wire cages in an air conditioned room without restraint during the experimental period. Two hours were allowed for acclimatization and determination of base line temperatures. S. enteriditis endotoxin was injected in the marginal ear vein and temperatures were deter mined every 30 minutes for an additional 61/2 hours. Temperatures were recorded on a Yellow Springs Telethermometer using thermocouples implanted deeply in the paraspinous muscles. Temperature curves were plotted on 1.0 cm graph paper with each centimeter representing 30 minutes and 0.5° (F.) temperature. The area above the base line was measured by an Ott Universal Planimeter and this reading was recorded as the fever index.