Phenolic Preservatives Are Not the Sole Cause of Eosinophilic Infiltration at Infusion Pump Sites

Background: Skin reactions and discomfort associated with insulin infusion pumps limit user adherence. A recent histopathological study by Kalus et al. (DERMIS study) reported increased eosinophilic infiltration and imputed an inflammatory response to an allergen delivered at the catheter tip. This finding might explain the pruritus reported by pump users. As eosinophils migrate to inflammatory foci, primarily due to IL-5 and CCL11, we aimed to evaluate insulin phenolic preservative (IPP) as a potential allergen in vitro and assess tissue eosinophilic infiltration in vivo. Methods: Histopathological evaluations for eosinophil recruitment were performed over 1 week following IPP infusions in swine tissue. Additional histopathological investigations of eosinophilic infiltration were conducted using three commercial glucose sensors implanted in swine for up to 3 weeks. Results: Eosinophilic infiltration in the dermis and subcutaneous tissue was observed following saline and IPP infusion and at glucose sensor implantation at all time points examined. In vitro studies revealed IPP eosinophil cytotoxicity. However, neither CCL11 nor IL-5 was detected in any of the tested tissue cells after IPP treatment. Conclusion: These findings suggest that IPP is not the only triggering allergen, as IPP did not induce eosinophils in vitro, while glucose sensors also indicated increased eosinophilic infiltration. Therefore, factors other than IPP trigger eosinophil recruitment to insulin infusion pump sets.