Neutropenic responses to intradermal injections of Escherichia coli. Effects on the kinetics of polymorphonuclear leukocyte emigration.

Killed Escherichia coli organisms injected intradermally into rabbits induced significant neutropenia and provoked a rapid rise in body temperature. Both the magnitude and the duration of the neutropenia were dose-dependent. After recovery from neutropenia, the rabbits became refractory to its redevelopment when subsequently given an equivalent dose of E coli. The influence of neutropenia and the subsequent refractory period on the rate of polymorphonuclear leukocyte (PMN) emigration into inflammatory sites was examined. Killed E coli organisms (6 X 10(8) per site) were injected into two groups of 20 intradermal sites in each rabbit. The first group (Group F) preceded the second (Group S) by 6 hours. The kinetics of PMN emigration, quantitated with 51Cr-labeled cells, differed in the two groups. In Group S sites an intense PMN influx was measured at 0-4 hours, and subsequently the extent of PMN emigration rapidly declined. In Group F sites a minute PMN influx was detected during the first 4 hours, coinciding with a marked neutropenia. The maximal PMN influx into Group F sites was measured between 6 and 10 hours. Microscopic sections at 4 hours showed a scanty PMN infiltrate and numerous bacteria in the dermis of Group F sites, while extensive phagocytosis of bacteria by PMNs was apparent in Group S sites. By comparing the extent of bacterial phagocytosis in 4-hour-old sites with the magnitudes of PMN emigration between 6 and 10 hours in both groups, we concluded that the phagocytic elimination of killed E coli was not a major mechanism regulating the cessation of local PMN emigration. Instead, we propose that tachyphylaxis or desensitization of sites to inflammatory factors released from E coli is the responsible mechanism.