E P Joslin Research Laboratory, Kidney and Hypertension Section, Joslin Diabetes Center, Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Boston and Cambridge, 521 Mount Auburn Street Watertown, MA 02472, USA. jd'
E P Joslin Research Laboratory, Kidney and Hypertension Section, Joslin Diabetes Center, Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Boston and Cambridge, 521 Mount Auburn Street Watertown, MA 02472, USA.
Int J Mol Sci. 2018 Aug 21;19(9):2465. doi: 10.3390/ijms19092465.
Immunosuppression may occur for a number of reasons related to an individual's frailty, debility, disease or from therapeutic iatrogenic intervention or misadventure. A large percentage of morbidity and mortality in immunodeficient populations is related to an inadequate response to infectious agents with slow response to antibiotics, enhancements of antibiotic resistance in populations, and markedly increased prevalence of acute inflammatory response, septic and infection related death. Given known relationships between intracellular calcium ion concentrations and cytotoxicity and cellular death, we looked at currently available data linking blockade of calcium ion channels and potential decrease in expression of sepsis among immunosuppressed patients. Notable are relationships between calcium, calcium channel, vitamin D mechanisms associated with sepsis and demonstration of antibiotic-resistant pathogens that may utilize channels sensitive to calcium channel blocker. We note that sepsis shock syndrome represents loss of regulation of inflammatory response to infection and that vitamin D, parathyroid hormone, fibroblast growth factor, and klotho interact with sepsis defense mechanisms in which movement of calcium and phosphorus are part of the process. Given these observations we consider that further investigation of the effect of relatively inexpensive calcium channel blockade agents of infections in immunosuppressed populations might be worthwhile.
免疫抑制可能由于个体虚弱、衰弱、疾病或治疗性医源性干预或意外而发生。免疫缺陷人群的发病率和死亡率很大一部分与对抗感染因子的反应不足有关，对抗生素的反应缓慢，人群中抗生素耐药性增强，急性炎症反应、败血症和感染相关死亡的患病率明显增加。鉴于细胞内钙离子浓度与细胞毒性和细胞死亡之间的已知关系，我们研究了目前可用的数据，这些数据将钙通道阻断与免疫抑制患者中败血症的潜在表达降低联系起来。值得注意的是，钙、钙通道、与败血症相关的维生素 D 机制之间的关系，以及可能利用对钙通道阻滞剂敏感的通道的抗生素耐药病原体的存在。我们注意到，败血症休克综合征代表对感染的炎症反应失去调节，维生素 D、甲状旁腺激素、成纤维细胞生长因子和 klotho 与败血症防御机制相互作用，其中钙和磷的移动是该过程的一部分。鉴于这些观察结果，我们认为进一步研究相对廉价的钙通道阻滞剂对免疫抑制人群感染的影响可能是值得的。
