Institute for Functional and Applied Anatomy, Hannover Medical School, Germany.
Ann Anat. 2011 Dec 20;193(6):486-93. doi: 10.1016/j.aanat.2011.10.009. Epub 2011 Oct 21.
Even now, sepsis remains a major problem in modern clinical medicine, leading to systemic inflammatory response including altered leukocyte subset distribution and increased cytokine release. As immune cells are known to express NPY receptors, we investigated the effects of a specific NPY Y(2) receptor agonist (NPY(13-36)) and/or the corresponding Y(2) receptor antagonist BIIE0246 treatment on blood (by FACS analyses) and tissue (by immunohistochemistry) leukocyte subsets as well as on levels of IL-4, IL-6, IL-10, TNF-α, INF-γ (by Cytometric Bead Array) in healthy and acutely endotoxemic rats. Results show a significant decrease in blood monocytes after LPS challenge in endotoxemic control animals (by 93%), in endotoxemic NPY(13-36) treated animals (by 83%) and in endotoxemic BIIE0246 treated animals (by 88%) as compared to the corresponding healthy controls. Endotoxemic control animals showed a significant increase of TNF-α (by 98%) as compared to the healthy control group. A treatment with NPY(13-36) significantly stabilized TNF-α level in endotoxemic animals. This study indicates distinct subset- and cytokine-specific in vivo effects induced by an NPY Y(2) receptor specific treatment after a short-term LPS challenge.
即使在现在，脓毒症仍然是现代临床医学中的一个主要问题，导致全身炎症反应，包括白细胞亚群分布改变和细胞因子释放增加。由于免疫细胞已知表达 NPY 受体，我们研究了特定的 NPY Y(2)受体激动剂（NPY(13-36)）和/或相应的 Y(2)受体拮抗剂 BIIE0246 对健康和急性内毒素血症大鼠血液（通过 FACS 分析）和组织（通过免疫组织化学）白细胞亚群以及白细胞介素-4、白细胞介素-6、白细胞介素-10、肿瘤坏死因子-α、干扰素-γ（通过细胞因子珠阵列）的影响。结果显示，内毒素血症对照动物的血液单核细胞在 LPS 挑战后显著减少（减少 93%），内毒素血症 NPY(13-36)治疗动物（减少 83%）和内毒素血症 BIIE0246 治疗动物（减少 88%）与相应的健康对照组相比。与健康对照组相比，内毒素血症对照动物的 TNF-α 显著增加（增加 98%）。用 NPY(13-36)治疗可显著稳定内毒素血症动物的 TNF-α 水平。这项研究表明，在短期 LPS 挑战后，NPY Y(2)受体特异性治疗会引起特定亚群和细胞因子的体内效应。
