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- Title
Hyperglycemia Exacerbates TH2 Immune Reactivity in a Cystic Fibrosis Related Diabetes Mouse Model.
- Authors
Stalvey, M.; Brusko, T.; Muller, C.; Wasserfall, C.; Schatz, D.; Flotte, T.; Atkinson, M.
- Abstract
Recent increases in life expectancy for patients with cystic fibrosis (CF) have paradoxically been accompanied by an increasing incidence of CF related diabetes (CFRD), which dramatically worsens prognosis. By a number of immunological parameter, CF alone is associated with a T[sub H]2 bias; potentially contributing to decreased macrophage host defense and hence, increasing the risk for prolonged infections. We tested the hypothesis that the development of hyperglycemia would exacerbate this T[sub H]2 bias through analysis of cystic fibrosis transmembrane conductance regulator deficient (CFTR-/-) mice; an animal model of CF. Nine CFTR-/-, 5 C57BL/6J, and 6 FVB/NJ mice received streptozotocin (STZ) (single dose of 100mg/kg) to induce hyperglycemia, while 8 CFTR-/-, 5 C57BL/6J, and 10 FVB/NJ mice received lactated fingers (LR). Four wk later, splenocytes were isolated, stimulated with Con-A, and cytokine production (48 hr) as well as stimulation indices (SI; 72 hr) determined. Four wk following STZ, CFTR-/- mice had greater fasting glucoses (CFTR.-/-288.4 ±97.4 mg/dL, C57BL/6J 154.2 ± 19.4, FVB/NJ 188 ± 42.26, p<0.05). SI of STZ-treated CFTR-/- mice were elevated compared to LR-treated CFTR-/- mice (p<0.05) as well as both STZ-treated and LR-treated control strains. Fasting glucose levels of STZ-treated CFTR-/- mice correlated with splenocyte proliferation (P<0.003). In terms of T[sub H]2 bias, concentrations of stimulated IL-10 were markedly elevated following the development of hyperglycemic induction in CFTR-/- mice compared to all controls (P<0.05). In addition, IL-4 was greater in CFTR-/- mice compared to controls (P<0.05), but no difference was observed between STZ and LR-treated CFTR-/- mice. These studies indicate hyperglycemia may indeed exacerbate the clinical course in CFRD by enhancing T[sub H]2 responses and provide additional, yet novel support for efforts seeking to maximize diabetes management in patients with this disorder.
- Subjects
CYSTIC fibrosis; DIABETES; LIFE expectancy; MACROPHAGES; HYPERGLYCEMIA; CYTOKINES; GLUCOSE; PEOPLE with diabetes; PATIENTS
- Publication
Diabetes, 2007, Vol 56, pA482
- ISSN
0012-1797
- Publication type
Article