Kinetics of acute inflammation induced by Escherichia coli in rabbits. II. The effect of hyperimmunization, complement depletion, and depletion of leukocytes.

The inflammatory response to Escherichia coli was quantitated in the skin of normal rabbits and the kinetics established as described previously. Hyperemia, measured with radiolabeled microspheres; vascular permeability, estimated with 125 I-albumin; and leukocyte infiltration, quantitated with 51Cr-labeled autologous leukocytes, reached maximal values 3 hours after the injection of bacteria and subsided almost completely by 6 hours. Hemorrhage, measured with homologous 59Fe-erythrocytes, continued to increase between 1 and 6 hours after injection and then reached plateau levels. The lesions were studied up to 8 hours, since in the previous study no changes were observed beyond that time. In the study described in this paper, the host mediation systems were manipulated in various groups of rabbits in order to elucidate the mechanisms underlying the development of the inflammatory reaction. One group of animals was hyperimmunized with the E coli organisms, another was partially depleted of hemolytic complement with cobra venom factor, and yet another was rendered leukopenic with nitrogen mustard. In hyperimmunized animals hyperemia in the dermal lesions induced by the microorganisms was significantly more intense than in normal rabbits. Vascular permeability increase occurred earlier in hyperimmunized rabbits and at 1 hour was significantly greater than in normals. Decomplemented rabbits had significantly less vascular permeability than normal animals, whereas in leukopenic rabbits no increase in vascular permeability could be elicited. Leukocyte accumulation was increased over the normal animals in the lesions of hyperimmunized rabbits. Hemorrhage was significantly decreased in leukopenic rabbits. Histologic examination of the lesions revealed that whereas in normal animals the infiltrating neutrophils ingested most of the bacteria and formed definite abscesses by 6-8 hours, these abscesses were absent in leukopenic animals, and free-lying bacteria were demonstrable in lesions. Histologically more neutrophils were present in the hyperimmunized than in the normal rabbits, but this difference was striking when normal animals were compared with leukopenic animals, in some of which only very occasional small accumulations of neutrophils were present.