Soft-tissue bacterial infection can progress to severe sepsis and septic shock as a result of a disproportionate inflammatory response, characterized by an excessive release of cytokines and influx of immune cells. Reltecimod (previously known as AB103 or p2TA), a peptide derived from the T-cell receptor CD28, modulates the host immune response by targeting the co-stimulatory pathway, which is essential for the induction of multiple pro-inflammatory cytokines. Consequently, reltecimod has demonstrated beneficial effects against different bacterial infections, their exotoxins and endotoxins, and ionizing radiation. The dosing regimen of reltecimod was evaluated in three mouse models of infection. The effect of the number of reltecimod doses with respect to survival, cytokine/chemokine levels, and blood leukocyte profiles was assessed. Overall, mice treated with a single intravenous dose of reltecimod (5 mg/kg) at 1–2 h after infection showed significantly greater survival as compared with saline-treated controls. Mice treated with a second doses demonstrated improved survival compared with saline-treated controls. However, in all models of infection, administration of a single therapeutic dose of reltecimod was superior to two or multiple doses. Further examination showed that the single therapeutic dose of reltecimod was associated with an early (within 24 h) decrease in cytokine/chemokine levels and most circulating leukocyte subpopulations. A second dose of reltecimod did not improve these early positive effects and appeared to attenuate further changes. These results provided insight into the mechanism of action of reltecimod and established a basis for the dosing regimen utilized in clinical trials, where reltecimod is administered as a single dose.

中文翻译：

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在致死性感染的小鼠模型中，一剂雷特莫德的治疗优于两剂

由于过度的炎症反应，其特征在于细胞因子的过度释放和免疫细胞的大量涌入，导致软组织细菌感染可发展为​​严重的败血症和败血性休克。Reltecimod（以前称为AB103或p2TA）是一种衍生自T细胞受体CD28的肽，它通过靶向共刺激途径来调节宿主的免疫反应，这对于诱导多种促炎性细胞因子至关重要。因此，相对于不同的细菌感染，其外毒素和内毒素以及电离辐射，reltecimod表现出了有益的作用。在三种感染小鼠模型中评估了reltecimod的给药方案。评估了reltecimod剂量数量对生存率，细胞因子/趋化因子水平和血液白细胞谱的影响。总体，与生理盐水对照组相比，在感染后1至2小时接受单次静脉注射reltecimod（5 mg / kg）治疗的小鼠，其存活率明显提高。与用盐水处理的对照相比，用第二剂处理的小鼠表现出改善的存活。但是，在所有感染模型中，一次治疗剂量的reltecimod的给药优于两次或多次给药。进一步检查显示，雷克替莫德的单次治疗剂量与细胞因子/趋化因子水平的早期下降（24小时之内）和大多数循环白细胞亚群有关。再次服用reltecimod并没有改善这些早期的积极作用，并且似乎减弱了进一步的改变。