Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Cytokine. 2012 May;58(2):307-15. doi: 10.1016/j.cyto.2012.01.017. Epub 2012 Mar 7.
Burn injuries together with its subsequent complications, mainly bacterial infections originating from gastrointestinal tract, activate the host immune system through stimulation of a series of local and systemic responses, including the release of inflammatory mediators. To gain a more comprehensive understanding of these complex physiological changes and to propose therapeutic approaches to combat the deleterious consequences of burn and septic shocks, it is essential to analyze animal models of burn and sepsis. In this study, we analyzed the long term profiles of cytokines and chemokines in rat models which received burn injury followed 2 days later by cecal ligation and puncture (CLP) to induce sepsis and were sacrificed at different time points within 10 days (0, 1, 2, 3, 4, 7 and 10 days). It was observed that MCP-1 concentrations were elevated in all animal models following the burn injury or CLP treatment. IP-10 concentration was persistently decreased after CLP or sham-CLP treatments. GRO/KC concentration was also increased following the burn injury and CLP. It was elucidated that, in more severe injury model which received both burn and CLP treatments, GMCSF and MIP-1α (chemokines), IL-1α (a pro-inflammatory cytokine) and IL-6 (exhibiting both pro- and anti-inflammatory behaviors) were upregulated on the 7th and 10th days, which might be to protect the host system from the subsequent complications caused by burn and sepsis. In order to elucidate critical regulatory interactions, putative transcription factors of the inflammatory mediators which have been significantly changed following the injuries were further identified by analyzing the conserved regions of the promoters of cytokines and chemokines. In conclusion, the long term profiles of the inflammatory mediators were profoundly characterized in this study to gain a comprehensive understanding of inflammatory mediators' behaviors in various injury models.
烧伤及其随后的并发症，主要是来自胃肠道的细菌感染，通过一系列局部和全身反应的刺激激活宿主免疫系统，包括炎症介质的释放。为了更全面地了解这些复杂的生理变化，并提出治疗方法来对抗烧伤和脓毒性休克的有害后果，分析烧伤和败血症的动物模型是至关重要的。在这项研究中，我们分析了接受烧伤损伤后 2 天接受盲肠结扎和穿刺（CLP）以诱导败血症并在 10 天内的不同时间点（0、1、2、3、4、7 和 10 天）处死的大鼠模型中的细胞因子和趋化因子的长期谱。观察到所有动物模型在烧伤损伤或 CLP 处理后 MCP-1 浓度升高。IP-10 浓度在 CLP 或假 CLP 处理后持续降低。GRO/KC 浓度在烧伤和 CLP 后也增加。阐明了在接受烧伤和 CLP 治疗的更严重损伤模型中，GMCSF 和 MIP-1α（趋化因子）、IL-1α（促炎细胞因子）和 IL-6（表现出促炎和抗炎行为）在第 7 天和第 10 天上调，这可能是为了保护宿主系统免受烧伤和败血症引起的后续并发症。为了阐明关键的调节相互作用，通过分析细胞因子和趋化因子启动子的保守区域，进一步鉴定了在损伤后明显变化的炎症介质的假定转录因子。总之，本研究深入描绘了炎症介质的长期谱，以全面了解各种损伤模型中炎症介质的行为。
