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Preservatives in insulin preparations impair leukocyte function. In vitro study.
I van Faassen1, A M Verweij-van Vught, M Z Lomecky-Janousek
1Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands.
Diabetes Care
|January 1, 1990
Summary
Insulin preservatives m-cresol and methyl p-hydroxybenzoate impair leukocyte function. M-cresol significantly reduced bacterial killing by leukocytes compared to methyl p-hydroxybenzoate, indicating it is more detrimental.
Area of Science:
- Immunology
- Pharmacology
- Diabetes Care
Background:
- Insulin preparations utilize preservatives like m-cresol and methyl p-hydroxybenzoate.
- Previous studies linked m-cresol containing insulin to increased infusion site inflammation in diabetic patients using continuous subcutaneous insulin infusion.
- Leukocyte function is critical for combating infections, especially in immunocompromised individuals like those with diabetes.
Purpose of the Study:
- To investigate the impact of insulin preservatives m-cresol and methyl p-hydroxybenzoate on leukocyte function.
- To compare the effects of these preservatives on the ability of leukocytes to kill bacteria.
- To assess how preservative concentration changes affect leukocyte function over time during insulin infusion.
Main Methods:
- Leukocyte function was assessed using a bacterial killing assay involving Staphylococcus aureus, polymorphonuclear leukocytes, serum, and insulin preparations.
- Insulin preparations with preservatives were tested before and after 1 and 4 days of perfusion through a PVC pump catheter to simulate infusion device interaction.
- Bacterial killing was quantified as the percentage of bacteria killed after 60 minutes of incubation.
Main Results:
- Insulin with m-cresol significantly reduced leukocyte bacterial killing compared to insulin without preservative (74.8-80.6% vs 95.4%).
- Insulin with methyl p-hydroxybenzoate also reduced bacterial killing (85.0-88.4%), but to a lesser extent than m-cresol.
- Perfusion through the pump catheter reduced preservative concentration but did not fully restore leukocyte killing capacity.
Conclusions:
- Both m-cresol and methyl p-hydroxybenzoate preservatives negatively impact leukocyte function, impairing their ability to kill bacteria.
- M-cresol demonstrates a more pronounced detrimental effect on leukocyte function compared to methyl p-hydroxybenzoate.
- These findings suggest that the choice of preservative in insulin formulations may influence immune response and infection risk at infusion sites.