We have developed a reproducible model of
granuloma formation in the mouse lung using a narrow size range (45-53 micron) of
divinyl benzene copolymer beads as a standard test material. Approximately 10,000 beads are given by
intravenous injection into the tail veins of mice whence they embolize to the lung and incite
granuloma formation. This delivery system eliminates the superimposed inflammatory reaction due to
trauma that occurs when materials are directly implanted at the test site by
surgical incision.
Granuloma size was quantitated at intervals from 3 h to 6 weeks by tracing mid-bead
granuloma areas on the ground glass screen of a light microscope at a known magnification and measuring the areas with a digitizer interfaced with a microcomputer programmed to prepare histograms and to merge data from replicate experiments. At 3 h only a few polymorphonuclear leukocytes could be observed adhering to the beads. At 48 h, the time of maximum
granuloma size (mean area = 7501 micron2), the
granulomas consisted of both polymorphonuclear and mononuclear leukocytes. After 6 weeks, the
granulomas were smaller, composed predominantly of mononuclear leukocytes and had a mean area of 2893 micron2. This model system allows the analysis of a large number of measurements, is reproducible, and provides a useful method for comparing the hosts' inflammatory response to a variety of potential
biomaterials, as well as for determining the effectiveness of antiinflammatory drugs.