Clinic of Neonatology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.
Scand J Clin Lab Invest. 2013 Aug;73(5):407-13. doi: 10.3109/00365513.2013.796591. Epub 2013 May 29.
In view of the central role of granulocytic neutrophils in the context of inflammatory reactions, the present study focuses on anti-inflammatory effects of drugs on activated neutrophils in neonates and adults.
Sixteen blood samples of neonates and adults were investigated in a prospective study. Loss of deformability, morphological changes, and increases in neutrophil elastase were determined as measures of neutrophil activation due to incubation with the pro-inflammatory cytokine interleukin-8. For inhibition experiments, the blood samples were also incubated with the phosphodiesterase inhibitors milrinone and piclamilast, the protease inhibitor urinastatin, ketamine, protein C concentrate, and the nitric oxide donor FK 409. Changes in deformability were investigated with a cell transit analyzer, morphological changes by microscopic observation, and the extent of neutrophil elastase release with an enzyme immunoassay.
The drugs milrinone, piclamilast, urinastatin, ketamine, protein C concentrate and FK 409 showed deactivating effects on activated neutrophils in recommended clinical doses. They improved deformability as well as reduced pseudopod formation and the release of neutrophil elastase. The effects on neutrophils did not differ between neonates and adults despite their functional differences.
We conclude that these drugs may reduce the inflammatory response and improve microcirculation in neonates and adults during inflammation.
鉴于中性粒细胞在炎症反应中的核心作用，本研究侧重于研究药物对新生儿和成人激活中性粒细胞的抗炎作用。
前瞻性研究中调查了 16 名新生儿和成人的血液样本。由于孵育促炎细胞因子白细胞介素-8，通过测定中性粒细胞的变形能力丧失、形态变化和中性粒细胞弹性蛋白酶的增加来确定中性粒细胞的激活。为了进行抑制实验，还将血液样本与磷酸二酯酶抑制剂米力农和匹拉米司他、蛋白酶抑制剂尿激酶原、氯胺酮、蛋白 C 浓缩物和一氧化氮供体 FK 409 一起孵育。用细胞转运分析仪研究变形能力的变化，用显微镜观察形态变化，用酶免疫测定法测定中性粒细胞弹性蛋白酶的释放量。
在推荐的临床剂量下，药物米力农、匹拉米司他、尿激酶原、氯胺酮、蛋白 C 浓缩物和 FK 409 对激活的中性粒细胞具有失活作用。它们改善了变形能力，减少了伪足形成和中性粒细胞弹性蛋白酶的释放。尽管新生儿和成人的功能存在差异，但它们对中性粒细胞的作用没有差异。
我们得出结论，这些药物可在炎症期间减轻新生儿和成人的炎症反应并改善其微循环。
