Anti-Inflammatory Protein Tumor Necrosis Factor-α-Stimulated Protein 6 (TSG-6) Promotes Early Gingival Wound Healing: An In Vivo Study

Background: Human multipotent mesenchymal stromal cells (hMSCs) produce tumor necrosis factor (TNF)-alpha-stimulated protein 6 (TSG-6). TSG-6 modulates proinflammatory cytokine cascades and enhances tissue repair. This study tests the effects of recombinant human TSG-6 (rhTSG-6) on gingival wound healing within the first 2 days post-surgery. Methods: After gingival resection in 120 Sprague-Dawley rats, 2 mu g rhTSG-6 in 5-mu L phosphate-buffered saline (PBS) or the same volume of only PBS solution was injected into gingival tissue approximating the surgical wound. Control animals did not receive injections. Tissue biopsies and blood were collected at 1 to 2, 6 to 8, 24, and 48 hours post-surgery (n = 10 per group). Specimens were analyzed via histologic analysis and enzyme-linked immunosorbent assay (ELISA) for quantification and comparison of inflammatory markers interleukin (IL)-1 beta, IL-6, TNF-alpha, and myeloperoxidase (MPO). Wound photographs were taken for a double-masked clinical assessment at each time period. Weights were recorded for all animals pre-and post-surgery. Results: Animals injected with rhTSG-6 had significantly less severe clinical inflammation at 6 to 8 (P = 0.01228), 24 (P = 0.01675), and 48 (P = 0.0186) hours. Sham and control animals had more weight loss at 24 and 48 hours. Sham and control animals had more pronounced cellular infiltrate. rhTSG-6-treated animals had significantly less MPO (P = 0.027) at 24 hours and IL-1 beta (P = 0.027) at 24 and 48 hours. IL-6 showed a marginal significant difference at 6 to 8 hours, but there was no significant difference for TNF-alpha. Conclusion: rhTSG-6 reduced postoperative gingival inflammation by reducing levels of proinflammatory cytokines and cellular infiltrate and may offer significant promise as an anti-inflammatory agent for gingival surgery.