Agarwal S, Piesco N P, Peterson D E, Charon J, Suzuki J B, Godowski K C, Southard G L
Division of Oral Biology and Dental Surgical Sciences, University of Pittsburgh School of Dental Medicine, PA 15261, USA.
J Periodontal Res. 1997 Apr;32(3):335-44. doi: 10.1111/j.1600-0765.1997.tb00542.x.
The effectiveness of an ideal antimicrobial agent depends on its ability to kill microbes with minimal toxicity to host cells. Depending on the treatment regimen, antimicrobial agents come into contact with host cells for various intervals of time. Sanguinarium (SANG), chlorhexidine (CHX) and tetracycline (TET) are 3 antimicrobial agents frequently used in the management of periodontal infections. However, their effects on host immune cells during different treatment regimens are not known. Due to their ability to serve as the first line of host defense against microbial infections, we have compared the effects of these antimicrobial agents on human neutrophil functions and viability. The results show that SANG is not lytic to neutrophils from peripheral blood or crevicular fluid, at all concentrations tested. However, exposures of neutrophils to very low concentrations of SANG (0.001%) inhibits neutrophil chemotaxis, oxidative metabolism and degranulation within 5 min. Increasing the exposure time results in a similar inhibition of neutrophil functions, albeit at 50-100 fold lower concentrations of SANG. CHX rapidly disrupts the cell membrane of both crevicular and peripheral blood neutrophils at concentrations above 0.005% within 5 min, and inhibition of all neutrophil functions is due to its lytic properties. While TET is least toxic to neutrophils, a dose dependent inhibition of neutrophil functions is dependent on the calcium concentrations of the cellular environment, and is observed only above 0.04% or higher concentrations in the absence of calcium. The data suggest that a critical cumulative concentration of these drugs is essential for their toxicity and inhibition of neutrophil functions. Therefore, both the length of exposure and the dose of the drug both are critical while considering the effectiveness of SANG, CHX or TET in the treatment of infections. Furthermore, due to differences in their mechanisms of action, the consequences of their effects on neutrophils may have significant bearing on tissue pathology as well as on their therapeutic efficacy.
理想抗菌剂的有效性取决于其杀灭微生物的能力，同时对宿主细胞的毒性要最小。根据治疗方案的不同，抗菌剂与宿主细胞接触的时间间隔也各不相同。血根碱（SANG）、洗必泰（CHX）和四环素（TET）是常用于治疗牙周感染的三种抗菌剂。然而，它们在不同治疗方案中对宿主免疫细胞的影响尚不清楚。由于中性粒细胞作为宿主抵御微生物感染的第一道防线，我们比较了这些抗菌剂对人中性粒细胞功能和活力的影响。结果表明，在所有测试浓度下，血根碱对来自外周血或龈沟液的中性粒细胞均无溶解作用。然而，将中性粒细胞暴露于极低浓度的血根碱（0.001%）中5分钟内，会抑制中性粒细胞的趋化性、氧化代谢和脱颗粒作用。延长暴露时间会导致对中性粒细胞功能的类似抑制，尽管血根碱的浓度要低50 - 100倍。洗必泰在浓度高于0.005%时，5分钟内会迅速破坏龈沟和外周血中性粒细胞的细胞膜，对所有中性粒细胞功能的抑制是由于其溶解特性。虽然四环素对中性粒细胞的毒性最小，但对中性粒细胞功能的剂量依赖性抑制取决于细胞环境中的钙浓度，并且仅在无钙情况下浓度高于0.04%或更高时才会观察到。数据表明，这些药物的临界累积浓度对于其毒性和抑制中性粒细胞功能至关重要。因此，在考虑血根碱、洗必泰或四环素治疗感染的有效性时，暴露时间和药物剂量都很关键。此外，由于它们作用机制的差异，它们对中性粒细胞作用的后果可能对组织病理学及其治疗效果都有重大影响。
