Differences in serum cytokine levels between wild type mice and mice with a targeted mutation suggests necessity of using control littermates

Abstract

To enhance protection from pathogens, housing conditions have been improved constantly. We wanted to test whether various environmental conditions and caging systems affect serum cytokine levels of immunodeficient mice differently than they affect immunocompetent control animals. We compared serum cytokine levels of immunodeficient and immunocompetent mice kept in three different environments: a specific pathogen free (SPF) breeding barrier with open cages. An SPF experimental unit with individually ventilated cages. An experimental semi-barrier with open cages. Serum from Rag1(-/-), μMT(-/-), IFN-γR(-/-), IFN-γ(-/-), IL-4(-/-), the heterozygous controls and wild type C57BL/6 or BALB/c mice was analyzed for the presence of 10 cytokines (IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, IFN-γ, TNF-α and GM-CSF). No major changes in cytokine levels were detected in mice exposed to different housing conditions. However, irrespective of immunodeficiency at 4 weeks of age a number of mice from the breeding colonies with a targeted mutation (TM), both -/- and +/- mice, showed a statistically significant elevation of some cytokines (primarily IL-1α, IL-5) when compared to wild type BALB/c and C57BL/6 mice. We conclude that under SPF conditions, immunodeficient mice can be kept either in open caging or IVC systems without affecting serum cytokine levels. The more important conclusion, however, stems from the observation that there is a significant difference in serum cytokine levels between wild type and mice carrying either one or two alleles of a targeted mutation (either -/- and +/- mice). This suggests an altered base-line inflammatory responsiveness in the TM-breeding colonies.