White W B, DeMartino S A, Yoshida T
Am J Med. 1983 May;74(5):909-14. doi: 10.1016/0002-9343(83)91085-9.
A diabetic patient had severe, delayed cutaneous reactions to insulin accompanied by fever, leukocytosis, and elevated erythrocyte sedimentation rate. Replacement of isophane beef-pork insulin suspension with other commercially available lente beef-pork, single-component beef and pork insulin preparations brought about no improvement. Intradermal testing demonstrated biphasic reactions to a wide variety of insulin preparations except for two recently available purified single-component (less than 1 ppm proinsulin) insulins. Immunologic studies showed increased incorporation of tritiated thymidine by the patient's peripheral blood lymphocytes after incubation with these insulin preparations that incited subcutaneous and intradermal reactions. Additionally, there was significant elaboration of the lymphokine, migration inhibitory factor, in response only to isophane beef-pork insulin. Control lymphocytes from a normal subject, from a patient with non-insulin-dependent diabetes, and from a patient with insulin-dependent diabetes without delayed allergy demonstrated no response to insulin preparations. The data suggest these delayed reactions were associated with a cellular immune response to one or more contaminants in the less purified insulin preparations.
一名糖尿病患者对胰岛素出现严重的延迟性皮肤反应，伴有发热、白细胞增多和红细胞沉降率升高。用其他市售的长效牛肉 - 猪肉胰岛素悬液、单组分牛肉和猪肉胰岛素制剂替代低精蛋白锌胰岛素牛肉 - 猪肉悬液后，病情并未改善。皮内试验表明，除了两种最近上市的纯化单组分（胰岛素原含量低于1 ppm）胰岛素外，患者对多种胰岛素制剂均出现双相反应。免疫学研究显示，患者外周血淋巴细胞在与引发皮下和皮内反应的胰岛素制剂孵育后，氚标记胸腺嘧啶核苷的掺入增加。此外，仅对低精蛋白锌胰岛素牛肉 - 猪肉悬液有显著的淋巴因子迁移抑制因子释放。来自正常受试者、非胰岛素依赖型糖尿病患者以及无延迟过敏的胰岛素依赖型糖尿病患者的对照淋巴细胞对胰岛素制剂无反应。数据表明，这些延迟反应与对纯化程度较低的胰岛素制剂中一种或多种污染物的细胞免疫反应有关。
