Severe delayed inflammatory reactions from injected insulin. Association with cell-mediated immunity

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.