对血液和脾脏中性粒细胞的功能以及庆大霉素治疗对其作用的研究:双重中和TNF-α和IL-1β并用庆大霉素治疗对金黄色葡萄球菌诱导的化脓性关节炎的改善作用的影响。
Impact of dual neutralization of TNF-α and IL-1β along with Gentamicin treatment on the functions of blood and splenic neutrophils and its role on improvement of S. aureus induced septic arthritis.
发表日期:2023 Aug 10
作者:
Sharmistha Ghosh, Rituparna Ghosh, Ritasha Sawoo, Puja Dutta, Biswadev Bishayi
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
近年的研究强调了抗生素改善化脓性关节炎的潜力,但由于多重耐药菌株如MRSA的快速出现,迫切需要新的替代治疗方法。本研究旨在探讨嗜中性粒细胞在调节S. aureus引起的化脓性关节炎炎症反应中的作用,同时使用TNF-α抗体或IL-1β抗体与庆大霉素或两者组合。本研究调查了抗氧化酶的作用,并与产生的ROS水平相关。通过免疫印迹评估了脾脏中TLR2、TNFR2、MMP2、RANKL、SAPK/JNK的表达情况。使用ELISA评估了血清IL-8、IL-10、IL-12、OPG、OPN、CRP的活性。流式细胞术研究评估了炎症中性粒细胞的数量。结果表明,TNF-α中和联合庆大霉素能够显著减轻关节肿胀。而联合治疗有效降低了血液中中性粒细胞ROS活性、精氨酸酶活性、MPO活性,同时减轻了脾脏中细菌负担。治疗组血清中的OPG、CRP、IL-10水平降低,而OPN、IL-8和IL-12水平增加,表明炎症损伤得到缓解。总体而言,这是一项新颖的研究,观察了抗生素和抗体治疗如何积极增强中性粒细胞功能以对抗败血症。由于本研究是在动物模型中进行的,可能不完全适用于临床试验。临床试验包括结晶性和炎症性关节炎、创伤、肿瘤等。在未来的研究中,放射学、骨科手术和动物系统反应的跨学科合作可能会为找到适当的治疗方法提供更好的思路。版权所有©2023 Elsevier B.V.。
Researches of recent past years have emphasized potential of antibiotics to improve septic arthritis but as multi-drug resistant strains like MRSA are emerging fast, new alternative therapeutic advances are high in demand. This study aims to figure out the role of neutrophils in regulating inflammatory responses of S. aureus induced septic arthritis while using TNF-α Ab or IL-1β Ab along with antibiotic gentamicin or both in combination. In this study, role of anti-oxidant enzymes were investigated and correlated with generated ROS level. While expression of TLR2, TNFR2, MMP2, RANKL, SAPK/JNK in the spleen were evaluated through western blot. Serum activity of IL-8, IL-10, IL-12, OPG, OPN, CRP was assessed using ELISA. Flow cytometry study evaluated inflamed neutrophil population. Results have shown TNF-α neutralization along with gentamicin was able to reduce arthritic swelling prominently. While combination therapy effectively reduced blood neutrophil ROS activity, arginase activity, MPO activity along with spleen bacterial burden. Serum OPG, CRP, IL-10 level got reduced while serum OPN, IL-8 and IL-12 level enhanced in treatment groups, showing mitigation of inflammatory damage. Overall, it is a novel work that observed how antibiotic and antibody therapy enhanced neutrophil function positively to combat sepsis. This study may not be fully applicable in clinical trials as it is performed with animal model. Clinical trials include crystalline and inflammatory arthritides, trauma, neoplasm. Interdisciplinary collaboration between radiology, orthopaedic surgery and knowledge of animal system responses may give better idea to find proper therapeutic approach in future research works.Copyright © 2023 Elsevier B.V. All rights reserved.