OBJECTIVE AND DESIGN Investigate survival outcomes, and immunological and metabolomic effects of hyaluronidase (Hz) treatment during mouse models of acute inflammation and sepsis. METHODS Survival of C57Bl/6 mice was monitored after lethal challenge with lipopolysaccharide (LPS) or cecal and ligation puncture (CLP)-induced sepsis and treated with Hz or saline. Mice were also challenged with LPS and treated with Hz for leukocyte counting, cytokine quantification and determination of metabolomic profiles in the peritoneal fluid. RESULTS Hz treatment improved survival outcomes after lethal challenge with LPS or CLP-induced sepsis. LPS challenge promoted acute neutrophil accumulation and production of interleukin-1β (IL-1β) and IL-6 in the peritoneum, whereas Hz treatment suppressed neutrophil infiltration and cytokine production. We further characterized the metabolomic alterations caused by LPS challenge, which predicted activity of metabolic pathways related to fatty acids and eicosanoids. Hz treatment had a profound effect over the metabolic response, reflected by reductions of the relative levels of fatty acids. CONCLUSION Collectively, these data demonstrate that Hz treatment is associated with metabolic reprogramming of pathways that sustain the inflammatory response.

中文翻译：

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透明质酸酶的免疫调节活性与急性炎症期间的代谢适应有关。

目的和设计 研究急性炎症和败血症小鼠模型中透明质酸酶 (Hz) 治疗的生存结果以及免疫学和代谢组学效应。方法 C57Bl/6 小鼠在用脂多糖 (LPS) 或盲肠和结扎穿刺 (CLP) 诱导的脓毒症进行致死性攻击后监测并用 Hz 或盐水治疗后的存活率。小鼠也用 LPS 进行攻击，并用 Hz 处理以进行白细胞计数、细胞因子定量和腹膜液中代谢组学特征的测定。结果 Hz 治疗改善了 LPS 或 CLP 诱导的脓毒症致死性攻击后的生存结果。LPS 刺激促进了腹膜中急性中性粒细胞的积累和白细胞介素 1β (IL-1β) 和 IL-6 的产生，而 Hz 治疗抑制了中性粒细胞浸润和细胞因子的产生。我们进一步表征了由 LPS 挑战引起的代谢组学改变，这预测了与脂肪酸和类花生酸相关的代谢途径的活性。Hz 处理对代谢反应有深远的影响，这反映在脂肪酸相对水平的降低上。结论 总的来说，这些数据表明，Hz 治疗与维持炎症反应的途径的代谢重编程有关。