Immunohistochemical Characterization of Specific Inflammatory Tissue Reactions following Embolization with Four Different Spherical Agents in the Minipig Kidney Model

Abstract

To evaluate the immunohistochemical inflammatory reaction after porcine renal embolization with the new spherical embolic agent Embozene and to compare it with other spherical embolic agents. After superselective porcine renal embolization (40 pigs) with different sizes of embolic agents (Embozene, Embosphere, Bead Block, Contour SE), tissue arrays were obtained (size ranges, 40-120 microm, 100-300 microm, 500-700 microm, 700-900 microm). After immunostaining for CD subtyping (CD45 and CD68) and cytokines (C-reactive protein [CRP] and interleukin-1 beta), a semiquantitative immunoreactivity score was calculated for each marker: intensity of staining was scored between 0 (negative) and 3 (intensive) and extent of staining between 0 and 4 (>80%), indicating the percentage of positive staining. The intensity score (0-3) was multiplied by the extent of staining score (0-4), resulting in a semiquantitative immunoreactivity score (0-12). Analysis of cellular expression profiles (ie, CD45, CD68) revealed a significantly higher inflammatory score 4 weeks after embolization with Embosphere 100-300 microm particles than after embolization with Embozene, Bead Block, and Contour SE. After 12 weeks, the Embosphere 100-300 microm score decreased. Analysis of CRP expression showed similar results, with a significantly higher score 4 weeks after embolization with Embosphere 100-300 microm. In the size class used most frequently for uterine artery emboliation (500-700 microm), all scores were low (<2.5) and there was no significant difference among particle types. Pronounced immunomarker expression was seen 4 weeks after embolization with small Embosphere particles. However, in general, modern spherical embolic agents cause a fairly low level of inflammatory reaction. In the present experimental setting, which is highly sensitive for specific tissue-to-agent reactivity, Embozene presented with low inflammatory results.