Continuous subcutaneous insulin infusion (CSII) and insulin antibodies in rabbits.
Using prepubertal male New Zealand White rabbits, continuous subcutaneous insulin infusion (CSII), delivered by either an external or an implantable infusion device, resulted in significantly higher insulin antibody (I-Ab) production than bolus injection (BII). We tested the influence during CSII of (1) the insulin species, (2) the insulin diluent, (3) the materials of which the infusion devices were made and (4) the incubation of insulin in a syringe on the backs of rabbits ('sham-infusion'), with the following results: (1) beef and sulphated beef insulins produced high levels of I-Abs, while porcine and human insulins produced moderate levels; (2) with all insulins used, 0.9% NaCl and 0.9% NaCl with 24-26 mmol NaHCO3 added, produced high levels of I-Ab. A buffer containing 0.7% NaCl, 0.136% sodium acetate trihydrate and 0.1% methyl-p-hydroxybenzoate and a buffer containing 16 mg/ml glycerol and 2 mg/ml phenol, produced highly significantly lower I-Abs (P less than 0.001); (3) insulin glass syringes produced much lower I-Ab levels than in standard polypropylene syringes and (4) polypropylene syringes in a 'sham-infusion' technique, resulted in intermediate levels of insulin antibodies [(P less than 0.02) vs CSII; (P less than 0.005) vs BII]. Our data suggest that insulin immunogenicity is influenced by all four factors tested. We suggest that benefits of CSII therapy may be attenuated unless a best possible control of these factors is achieved.