Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Cytokine. 2011 Sep;55(3):362-71. doi: 10.1016/j.cyto.2011.05.010. Epub 2011 Jun 8.
The inflammatory response, and its subsequent resolution, are the result of a very complex cascade of events originating at the site of injury or infection. When the response is severe and persistent, Systemic Inflammatory Response Syndrome can set in, which is associated with a severely debilitating systemic hypercatabolic state. This complex behavior, mediated by cytokines and chemokines, needs to be further explored to better understand its systems properties and potentially identify multiple targets that could be addressed simultaneously. In this context, short term responses of serum cytokines and chemokines were analyzed in two types of insults: rats receiving a "sterile" cutaneous dorsal burn on 20% of the total body surface area (TBSA); rats receiving a cecum ligation and puncture treatment (CLP) to induce infection. Considering the temporal variability observed in the baseline corresponding to the control group, the concept of area under the curve (AUC) was explored to assess the dynamic responses of cytokines and chemokines. MCP-1, GROK/KC, IL-12, IL-18 and IL-10 were observed in both burn and CLP groups. While IL-10 concentration was only increased in the burn group, Eotaxin was only elevated in CLP group. It was also observed that Leptin and IP-1 concentrations were decreased in both CLP and sham-CLP groups. The link between the circulating protein mediators and putative transcription factors regulating the cytokine/chemokine gene expression was explored by searching the promoter regions of cytokine/chemokine genes in order to characterize and differentiate the inflammatory responses based on the dynamic data. Integrating multiple sources together with the bioinformatics tools identified mediators sensitive to type and extent of injury, and provided putative regulatory mechanisms. This is essential to gain a better understanding for the important regulatory points that can be used to modulate the inflammatory state at molecular level.
炎症反应及其随后的解决是源自损伤或感染部位的非常复杂级联事件的结果。当反应严重且持续时，可能会出现全身炎症反应综合征，这与严重的全身性高分解代谢状态有关。这种由细胞因子和趋化因子介导的复杂行为需要进一步探索，以更好地了解其系统特性，并有可能同时确定多个可以同时处理的目标。在这种情况下，分析了两种类型的刺激下血清细胞因子和趋化因子的短期反应：在 20%的总体表面积（TBSA）上接受“无菌”皮肤背部烧伤的大鼠；接受盲肠结扎和穿刺治疗（CLP）以诱导感染的大鼠。考虑到对照组基线观察到的时间可变性，探索了曲线下面积（AUC）的概念，以评估细胞因子和趋化因子的动态反应。在烧伤和 CLP 组中均观察到 MCP-1、GROK/KC、IL-12、IL-18 和 IL-10。虽然仅在烧伤组中观察到 IL-10 浓度增加，但仅在 CLP 组中观察到 Eotaxin 升高。还观察到 Leptin 和 IP-1 浓度在 CLP 和假 CLP 组中均降低。通过搜索细胞因子/趋化因子基因的启动子区域，探索了循环蛋白介质与调节细胞因子/趋化因子基因表达的潜在转录因子之间的联系，以根据动态数据对炎症反应进行特征描述和区分。将多个来源与生物信息学工具相结合，确定了对损伤类型和程度敏感的介质，并提供了潜在的调节机制。这对于更好地理解可以在分子水平上调节炎症状态的重要调节点至关重要。
