Han Dennis P
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Trans Am Ophthalmol Soc. 2004;102:305-20.
To test the feasibility of human immune globulin (IG, Gamimune N, 10%) as a new treatment for endophthalmitis, the ocular tolerance, distribution, and ability of intravitreal IG to attenuate the toxic effects of Staphylococcus aureus culture supernatant were evaluated in a rabbit model.
Effects of intravitreally injected IG were assessed histologically and with Western blot analysis performed 1 to 5 days after injection. IG reactivity to products of S. aureus strain RN4220 was tested by Western blotting, using known toxins (beta hemolysin and toxic shock syndrome toxin-1) and a concentrated culture supernatant containing S. aureus exotoxins (pooled toxin, PT). Endophthalmitis was induced by intravitreal PT injection. For treatment, IG and PT were mixed and injected simultaneously, or IG was injected immediately after, or 6 hours after, PT injection. PT toxicity was graded clinically and histologically over 9 days.
IG persisted intravitreally at least 5 days, inducing no clinical inflammation and minimal mononuclear cell infiltration. In the endophthalmitis model, toxicity from PT was significantly reduced when IG was mixed with PT and injected simultaneously, or when IG was delivered immediately after PT. Only minimal clinically detectable reductions were observed when IG delivery was delayed 6 hours.
Intravitreal IG is well tolerated in the rabbit eye and attenuates the toxicity of culture supernatant containing S. aureus exotoxins. Because toxin elaboration likely occurs gradually in true infection, reduced effects observed with delayed treatment in this toxin-injected model do not preclude clinical application. IG may represent a novel adjunct in endophthalmitis treatment.
为了测试人免疫球蛋白（IG，Gamimune N，10%）作为眼内炎新治疗方法的可行性，在兔模型中评估了玻璃体内注射IG的眼内耐受性、分布以及减轻金黄色葡萄球菌培养上清液毒性作用的能力。
在注射后1至5天，通过组织学和蛋白质印迹分析评估玻璃体内注射IG的效果。使用已知毒素（β溶血素和中毒性休克综合征毒素-1）以及含有金黄色葡萄球菌外毒素的浓缩培养上清液（混合毒素，PT），通过蛋白质印迹法检测IG对金黄色葡萄球菌RN4220菌株产物的反应性。通过玻璃体内注射PT诱导眼内炎。对于治疗，将IG和PT混合并同时注射，或者在PT注射后立即或6小时后注射IG。在9天内对PT毒性进行临床和组织学分级。
IG在玻璃体内至少持续存在5天，未引起临床炎症且单核细胞浸润极少。在眼内炎模型中，当IG与PT混合并同时注射，或者在PT注射后立即注射时，PT的毒性显著降低。当IG注射延迟6小时时，仅观察到临床上可检测到的最小程度降低。
玻璃体内注射IG在兔眼中耐受性良好，并可减轻含有金黄色葡萄球菌外毒素的培养上清液的毒性。由于在真正感染中毒素的产生可能是逐渐发生的，在这个注射毒素的模型中延迟治疗观察到的效果降低并不排除临床应用。IG可能是眼内炎治疗中的一种新型辅助药物。
