Sriskandan Shiranee, Ferguson Melissa, Elliot Victoria, Faulkner Lee, Cohen Jonathan
Department of Infectious Diseases, Imperial College London, Hammersmith Hospital Du Cane Road, London W12 0NN, UK.
J Antimicrob Chemother. 2006 Jul;58(1):117-24. doi: 10.1093/jac/dkl173. Epub 2006 May 2.
Polyclonal human intravenous immunoglobulin (IVIG) has been advocated as an adjunct to therapy in severe invasive streptococcal toxic shock because of its ability to neutralize superantigen toxins. The aim of this study was to assess IVIG therapeutic efficacy in an experimental model of streptococcal toxic shock.
To confirm the in vitro activity of IVIG against the Streptococcus pyogenes strain used in the study, IVIG was tested for superantigen neutralizing and bacterial opsonizing activity prior to in vivo studies. To evaluate the in vivo effects of IVIG in terms of microbiological outcome and disease severity in a superantigen-sensitive transgenic model of streptococcal shock, HLA-DQ transgenic mice were treated with IVIG either at the time of infection or after infection with S. pyogenes. Antibiotics were included in some studies.
The IVIG preparation neutralized superantigenicity of S. pyogenes in vitro and enhanced bacterial killing in a whole blood assay. When given to mice at the time of S. pyogenes infection, IVIG neutralized circulating superantigens and reduced systemic inflammatory response. Remarkably, IVIG-enhanced systemic clearance of bacteria and enhanced neutrophil infiltrate into the infected tissues. However, when used in combination with penicillin and clindamycin in a delayed treatment setting, IVIG did not confer additional therapeutic benefit, in terms of inflammatory response, bacterial clearance or survival.
IVIG monotherapy can confer benefit in experimental streptococcal shock, but extension of these findings to the clinical situation will require further evaluation.
多克隆人静脉注射免疫球蛋白（IVIG）因具有中和超抗原毒素的能力，被提倡作为重症侵袭性链球菌中毒性休克治疗的辅助手段。本研究的目的是评估IVIG在链球菌中毒性休克实验模型中的治疗效果。
为确认IVIG对研究中所用化脓性链球菌菌株的体外活性，在进行体内研究之前，对IVIG进行了超抗原中和及细菌调理活性测试。为评估IVIG在超抗原敏感的链球菌休克转基因模型中对微生物学结果和疾病严重程度的体内影响，在感染化脓性链球菌时或感染后，对HLA-DQ转基因小鼠用IVIG进行治疗。部分研究中包含了抗生素。
IVIG制剂在体外中和了化脓性链球菌的超抗原性，并在全血试验中增强了细菌杀伤作用。在化脓性链球菌感染时给予小鼠IVIG，可中和循环中的超抗原并减轻全身炎症反应。值得注意的是，IVIG增强了细菌的全身清除，并增强了中性粒细胞向感染组织的浸润。然而，在延迟治疗中与青霉素和克林霉素联合使用时，IVIG在炎症反应、细菌清除或生存方面并未带来额外的治疗益处。
IVIG单一疗法在实验性链球菌休克中可带来益处，但要将这些发现推广至临床情况还需要进一步评估。
