Bettinger D A, Pellicane J V, Tarry W C, Yager D R, Diegelmann R F, Lee R, Cohen I K, DeMaria E J
Division of General Surgery, Medical College of Virginia Hospitals/Virginia Commonwealth University, Richmond 23298-1773.
J Trauma. 1994 Jun;36(6):810-3; discussion 813-4. doi: 10.1097/00005373-199406000-00010.
The role of cytokines in normal wound healing remains poorly defined. In vitro, tumor necrosis factor alpha (TNF-alpha) decreases collagen accumulation, perhaps by increasing collagenase activity. The current study was undertaken to test the hypothesis that cytokines impair wound healing and collagen production. Wounds in C3H/HeJ (J) mice, which are characterized by a genetic defect in macrophage production of TNF and other cytokines in response to endotoxin, were compared with wounds in normal endotoxin-sensitive C3H/HeN (N) mice.
TNF (by murine ELISA) and collagenolytic activity (CA by in vivo labelled collagen fibril degradation assay) were measured in wound fluid from silicone reservoirs on post-wounding days 1, 3, and 5 (n = 5 per group). Hydroxyproline (HOP, nmol/mg sponge) incorporation (by HPLC) in polyvinylacohol sponges and breaking strength (BS, as determined by tensiometry) in linear wounds were assessed on days 5, 7, 10, and 14 (n = 5 per group). The data demonstrate significantly increased BS at 5 and 7 days in endotoxin-resistant J mice compared with that in endotoxin-sensitive N mice. An early, significant reduction in TNF production in J mice corresponded with a significant increase in CA on day 1, increased collagen production at day 7, and increased procollagen gene transcription at early time points. Conclusion. The reduced production of inflammatory cytokines including TNF in the wound fluid of J mice corresponded with an early improvement in wound tensile strength. An accelerated accumulation of collagen in the wounds of J mice, perhaps resulting from a significant decrease in collagenolytic activity or increased collagen production, are potential mechanisms. The data suggest that cytokines produced in normal healing of clean wounds may contribute to a delay in increased tensile strength.
细胞因子在正常伤口愈合中的作用仍不清楚。在体外，肿瘤坏死因子α（TNF-α）可能通过增加胶原酶活性来减少胶原蛋白的积累。本研究旨在验证细胞因子会损害伤口愈合和胶原蛋白生成这一假说。将C3H/HeJ（J）小鼠（其特征是巨噬细胞对内毒素产生TNF和其他细胞因子存在基因缺陷）的伤口与正常的对内毒素敏感的C3H/HeN（N）小鼠的伤口进行比较。
在受伤后第1、3和5天，测量来自硅胶储液器的伤口液中的TNF（通过小鼠ELISA法）和胶原olytic活性（通过体内标记胶原纤维降解试验测定的CA）（每组n = 5）。在第5、7、10和14天评估聚乙烯醇海绵中羟脯氨酸（HOP，nmol/mg海绵）的掺入量（通过HPLC）和线性伤口的断裂强度（BS，通过张力测定法测定）（每组n = 5）。数据显示，与内毒素敏感的N小鼠相比，内毒素抗性J小鼠在第5天和第7天的BS显著增加。J小鼠中TNF产生的早期显著减少与第1天CA的显著增加、第7天胶原蛋白生成的增加以及早期时间点前胶原基因转录的增加相对应。结论。J小鼠伤口液中包括TNF在内的炎性细胞因子产生减少与伤口抗张强度的早期改善相对应。J小鼠伤口中胶原蛋白的加速积累，可能是由于胶原olytic活性的显著降低或胶原蛋白生成增加，是潜在的机制。数据表明，清洁伤口正常愈合过程中产生的细胞因子可能导致抗张强度增加的延迟。
