Impact of Proinflammatory Cytokine Knockout on Mesh Integration

Abstract

Placement of mesh is involved in 75–80% of hernia operations. It is known that an exaggerated foreign body reaction leads to clinical complications. To further improve patients outcome using biotechnological agents targeted against tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6), a study was conducted investigating the impact of cytokine knockout on mesh integration. Sixty mice were used: C57BL/6 wild type control, C57BL/6-IL-6 interleukin-6 knockout, C57BL/6-Tnfrsf1a knockout of TNF-α receptor 1, and C57BL/6-Tnfrsf1b knockout of TNF-α receptor 2. Standard polypropylene mesh was implanted subcutaneously for 7, 21, and 90 days. The inflammatory and connective tissue formation was characterized by diameter of inner cellular infiltrate and outer fibrous capsule of the foreign body granuloma, and by quantity (collagen/protein ratio) and quality (collagen type I/III ratio) of collagen formation. Microscopic investigation of the mesh/host-tissue interface showed typical formation of foreign body granulomas. Ninety days after implantation none of the knockout strains showed significant differences compared to the control group investigating amount of inflammatory and connective tissue formation. Analyzing the quantity of filamentary collagen deposition the C57BL/6-IL-6 group showed significant lowered values compared to the control group 90 days after implantation. In all groups collagen type I/III ratio increased over time as an indicator for maturation of the surrounding collagen formation. However, no difference was found comparing strains at the end of the observation period. The results support the notion that wound healing is affected by cytokine deficiency. However, a desirable reduced amount of inflammatory tissue formation as well as an increased collagen type I/III ratio due to cytokine knockout could not be observed.