IngentaConnect A murine model of appendicitis and the impact of inflammation on ...

Abstract:

Summary

Data indicate that appendicectomy for intra-abdominal inflammation protects against inflammatory bowel disease (IBD). This suggests an important role for the appendix in mucosal immunity. There is no established model of appendicitis. We therefore developed a murine model of appendicitis and examined the effect of inflammation on appendiceal lymphocyte constituents. The caecal patch of specific pathogen-free (SPF)-Balb/c mice was transformed into an obstructed `appendiceal pouch' by standardized suction and band ligation. Mice were killed and `pouches' removed for histology and phenotypic analysis of leucocytes by flow cytometry. Serum C-reactive protein (CRP) was determined by enzyme-linked immunosorbent assay. All `pouches' developed features resembling human appendicitis - mucosal ulceration, transmural inflammation with neutrophils, lymphocytes and occasional eosinophils, and serositis. These changes were most evident between days 7 and 10. There was significant elevation of serum CRP (8·0 ± 0·3 ng/ml to 40·0 ± 3·1 ng/ml; P < 0·01), indicating systemic inflammation. Following the initial neutrophil-predominant response, there was an increase in CD4⁺ (15·3% ± 1·2% to 31·0 ± 2·0%; P < 0·01) and CD8⁺ T lymphocytes (3·7% ± 0·6% to 9·2 ± 0·8%; P < 0·01). CD25⁺ forkhead box P3 (FoxP3)⁺ regulatory T lymphocytes were increased by 66% (P < 0·01). Furthermore, significant increases in CD8⁺ FoxP3⁺ regulatory T lymphocytes were restricted to younger mice (age < 10 weeks, P < 0·003). This is the first description of a murine model of appendicitis. Inflammation resulted in T lymphocyte accumulation associated with an increase in regulatory T lymphocytes, which might explain the age-dependent protective phenomenon. Further exploration will provide insights into the mechanisms of intestinal immune homeostasis and the immunopathogenesis of IBD.

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A murine model of appendicitis and the impact of inflammation on appendiceal lymphocyte constituents