Elevated mucosal
IL-12/23p40 and IFN-gamma accompany early
inflammation in IL-10-deficient (IL-10(-/-)) mice and then later decline while
inflammation persists. This report addresses whether this
cytokine profile reflects
disease progression or inherent, age-related changes in mucosal immunity. IL-10(-/-) and wild-type (WT) mice were maintained in an ultrabarrier facility or transferred to conventional housing at 3, 12, or 30 weeks of age. Weight, stool changes, and histologic features were followed. Lamina propria mononuclear cells were cultured for
cytokine analysis by ELISA. Ultrabarrier-housed IL-10(-/-) mice are statistically indistinguishable from WT mice by weight, disease activity index, and histologic
inflammation. IL-10(-/-) mice but not WT, transferred at 3 weeks, develop
colitis gradually, reaching a significant, sustained maximum by 15 weeks of age. Transfer at 12 weeks induces rapid disease onset in both strains, maximal at 15 weeks of age.
Inflammation persists in IL-10(-/-), and WT recover. IL-10(-/-) and WT mice transferred at 30 weeks demonstrate transient
diarrhea and
weight loss but no chronic
inflammation. Probiotics delay symptom onset only in the 12-week-old group. IFN-gamma production from ultrabarrier-housed IL-10(-/-) mice is elevated at 12 weeks of age, and older animals have decreased IFN-gamma and increased
IL-4.
IL-10 is important for suppressing
inflammation after transfer at 3 weeks of age and limiting
inflammation after transfer at 12 weeks but has little influence at 30 weeks of age.
Colitis onset, progression, and response to probiotic
therapy vary with immune system age, suggesting that a distinct, Th1-driven, age-dependent
cytokine profile may contribute to increased
colitis susceptibility in otherwise healthy mice.