Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
Graduate School of Medical Science & Engineering, KAIST, Daejeon, Republic of Korea.
PLoS One. 2019 May 14;14(5):e0216926. doi: 10.1371/journal.pone.0216926. eCollection 2019.
Silicone is used widely for tissue augmentation in humans. However, late complications, such as delayed inflammation and capsular contracture, remain uncharacterized, despite their importance. In the present study, we aimed to determine whether mechanical and thermal damage induce capsular inflammation around a foreign body, and elucidate the biological mechanism underlying this phenomenon. We injected silicone into the subcutaneous layer of the skin of New Zealand white rabbits. The rabbits were divided into two groups: the control group received no treatment; in the experimental group, external force was applied near the injection silicone using high-intensity focused ultrasound (HIFU). Tissues near the injected silicone were harvested from both groups on Days 4, 7, and 30 after HIFU treatment for comparative analysis. Visual and histological examinations showed clearly increased inflammation in the experimental group compared with that in the control group. Furthermore, capsular tissue from the experimental group displayed markedly increased collagen production. Immunofluorescence revealed marked activation of macrophages in the early stages of inflammation (Days 4 and 7 after HIFU treatment), which decreased on Day 30. Assessment of cytokine activation showed significantly increased expression of heat shock protein (HSP)27, HSP60, HSP70, toll-like receptor (TLR)2, TLR4, and interleukin-8 in the experimental group. The expression of transforming growth factor-β1 did not increase significantly in the experimental group. In conclusion, damage to tissues around the injected silicone induced capsular inflammation. Macrophages and damage-associated molecular pattern molecules were involved in the early stages of inflammation. HSP release activated TLRs, which subsequently activated innate immunity and induced the inflammatory response.
硅树脂在人体组织增强中被广泛应用。然而，尽管这些并发症很重要，但迟发性炎症和包膜挛缩等晚期并发症仍未得到明确描述。在本研究中，我们旨在确定机械和热损伤是否会引起异物周围的包膜炎症，并阐明其潜在的生物学机制。我们将硅树脂注入新西兰白兔的皮下层。将兔子分为两组：对照组未接受任何治疗；实验组在注射硅树脂附近使用高强度聚焦超声（HIFU）施加外力。在 HIFU 治疗后第 4、7 和 30 天，从两组采集注射硅树脂附近的组织进行比较分析。肉眼和组织学检查显示实验组的炎症明显高于对照组。此外，实验组的包膜组织显示出明显增加的胶原蛋白生成。免疫荧光显示，在炎症的早期阶段（HIFU 治疗后第 4 和第 7 天），巨噬细胞明显活化，而在第 30 天则减少。细胞因子激活评估显示，实验组中热休克蛋白（HSP）27、HSP60、HSP70、Toll 样受体（TLR）2、TLR4 和白细胞介素-8 的表达明显增加。实验组中转化生长因子-β1 的表达没有明显增加。总之，注射硅树脂周围组织的损伤会引起包膜炎症。巨噬细胞和损伤相关分子模式分子参与了炎症的早期阶段。HSP 释放激活了 TLRs，随后激活了固有免疫并诱导了炎症反应。
