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THE AGING MUCOSAL IMMUNE SYSTEM IN THE INTERLEUKIN-10-DEFICIENT MOUSE

Etling, Michele R
http://rave.ohiolink.edu/etdc/view?acc_num=case1184295867

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Pathology.
Elevations in the mucosal expression of IFN-γ and the common p40 subunit of IL-12 and IL-23 accompany early colonic inflammation in interleukin-10 deficient (IL-10 ‑/‑) mice. These cytokines later decline while inflammation persists. Changes in the immune response are known to occur as a component of normal aging, and have been shown to affect disease course in multiple systems. I therefore hypothesized that age-associated variations in systemic and mucosal expression of multiple cytokines in the IL-10 ‑/‑mouse reflect underlying age-related alterations in systemic and mucosal immunity. To address this question, IL-10 ‑/‑and wild-type mice were maintained in an ultrabarrier facility or transferred to conventional housing at 3, 12, or 30 weeks of age, with or without pretreatment with probiotic organisms. Weight, stool changes, and histologic features were followed. Lamina propria mononuclear cells were cultured for cytokine analysis by ELISA or multiplex cytokine array. Ultrabarrier-housed IL-10 ‑/‑mice were found to be statistically indistinguishable from wild-type mice by weight, disease activity index, and histologic inflammation. In addition, IL-10 ‑/‑mice, but not wild-type, transferred at 3 weeks gradually develop colitis, reaching 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 ‑/‑, while wild-types recover. IL-10 ‑/‑and wild-type mice transferred at 30 weeks demonstrate transient diarrhea and weight loss, but no chronic inflammation. Probiotics delay symptom onset only in 12-week-old group. Age-associated fluctuations in systemic and mucosal levels of several cytokines were found in both IL10 ‑/‑and wild-type mice, and expression of many cytokines was elevated even in the absence of overt disease. LPS induced higher levels of IFN-γ from IL-10 ‑/‑ versusWT splenocytes, but IL-17 increaed with TCR stimulation. These experiments demonstrated that IL-10 is important for suppressing inflammation after transfer at 3 weeks of age, and in 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 underlying abnormalities in the expression of multiple cytokines may contribute to increased colitis susceptibility in otherwise healthy mice.
Alan Levine (Advisor)
168 p.
Health Sciences, Immunology
Immunology; Inflammatory Bowel Disease; Aging; Interleukin 10 deficient mouse; Cytokines; Probiotics

Recommended Citations

Citations

  • Etling, M. R. (2007). THE AGING MUCOSAL IMMUNE SYSTEM IN THE INTERLEUKIN-10-DEFICIENT MOUSE [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1184295867

    APA Style (7th edition)

  • Etling, Michele. THE AGING MUCOSAL IMMUNE SYSTEM IN THE INTERLEUKIN-10-DEFICIENT MOUSE. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1184295867.

    MLA Style (8th edition)

  • Etling, Michele. "THE AGING MUCOSAL IMMUNE SYSTEM IN THE INTERLEUKIN-10-DEFICIENT MOUSE." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1184295867

    Chicago Manual of Style (17th edition)

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© 2007, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.
Release 3.2.12