Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Norwida 31, PL 50-375 Wrocław, Poland.
Pharmacol Rep. 2011;63(6):1481-90. doi: 10.1016/s1734-1140(11)70712-5.
The low-molecular weight dipeptide bestatin is a potent inhibitor of aminopeptidase N and has been demonstrated to have antitumor and immunomodulatory effects. The effects of bestatin on interleukin (IL)-1β synthesis and release by peritoneal macrophages stimulated in vitro with lipopolysaccharide (LPS) from E. coli, the phagocytic and oxidative burst activity from peripheral blood monocytes and granulocytes and the number of blood leukocytes and blood picture in cyclophosphamide-treated mice were tested. Bestatin at doses of 1 and 0.1 mg/kg was injected into cyclophosphamide-treated mice ip five times on alternating days or ten times at 24 h intervals. The first dose of bestatin was administered 24 h after a single injection of cyclophosphamide at a dose of 350 mg/kg. It was found that bestatin administered at doses of 1 and 0.1 mg/kg five times on alternating days increased the synthesis and release of IL-1β by resident peritoneal murine macrophages stimulated in vitro with LPS in cyclophosphamide-treated mice. The immunocorrecting action of bestatin on the picture of peripheral blood in cyclophosphamide-treated mice was primarily observed with young forms of neutrophilic granulocytes. The changes were observed irrespective of the dosage and the number of subsequent doses applied. Moreover, the administration of bestatin after pharmacological immunosuppression partially prevented the suppressive effects of cyclophosphamide on the oxidative burst activity of peripheral blood monocytes and stimulated the phagocytic activity of granulocytes.
小分子二肽贝他斯汀是一种有效的氨肽酶 N 抑制剂，已被证明具有抗肿瘤和免疫调节作用。本研究检测了贝他斯汀对大肠杆菌脂多糖（LPS）体外刺激的腹腔巨噬细胞白细胞介素（IL）-1β合成和释放、外周血单核细胞和粒细胞的吞噬和氧化爆发活性以及环磷酰胺处理小鼠的白细胞数量和血象的影响。贝他斯汀以 1 和 0.1 mg/kg 的剂量腹腔注射至环磷酰胺处理的小鼠中，每两天交替注射五次或每隔 24 h 注射十次。贝他斯汀的第一次剂量在环磷酰胺（350 mg/kg）单次注射后 24 h 给予。结果发现，贝他斯汀以 1 和 0.1 mg/kg 的剂量，每两天交替注射五次，可增加 LPS 体外刺激的环磷酰胺处理小鼠腹腔驻留巨噬细胞中 IL-1β的合成和释放。贝他斯汀对环磷酰胺处理小鼠外周血象的免疫纠正作用主要观察到年轻的中性粒细胞。无论剂量和随后应用的剂量数如何，均观察到这些变化。此外，贝他斯汀在药理学免疫抑制后给药部分预防了环磷酰胺对外周血单核细胞氧化爆发活性的抑制作用，并刺激了粒细胞的吞噬活性。
