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Active Crohn's disease and ulcerative colitis evaluated by magnetic resonance imaging

1998; Elsevier BV; Volume: 114; Linguagem: Inglês

10.1016/s0016-5085(98)84191-7

1528-0012

SM Madsen, HS Thomsen, Pia Munkholm, S. Dorph, P. Schlichting,

Diagnosis and treatment of tuberculosis

Background: We have previously shown that IL-10 gene deficient mice have a primary defect in secretion of secretory IgA (slgA) into breast milk.These mice also demonstrate increased levels of aerobic and anaerobic adherent bacteria in the colon and develop a colitis, histologically similar to Crohn's disease.Aim: The purpose of this study was to determine whether the breast milk, with its low levels of slgA, played a role in the increased levels of adherent bacteria seen at 2 wks of age, and the subsequent development of colitis at 4 wk of age in the IL-10 gene deficient mouse.Methods: IL-10 gene deficient (KO) and normal control (C) mice were raised under virus antibody-free conditions.Within 24 hours of birth, IL-10 genedeficient pups were cross-fostered to normal control mothers (XFKO), and normal control pups were cross-fostered to IL-10 gene-deficient mothers (XFC).Mice were weaned at 3 wk of age.Colon, harvested from 2, 4, and 8 wk old mice, was cultured for adherent bacteria and histologic injury scored (0 to 10).Results were compared with normal controls (C) and IL-10 genedeficient (KO) mice.Results: At 2 wks of age, normal control pups cross-fostered to an IL-10 gene-deficient mother (XFC) had significantly increased levels of aerobic and anaerobic colonic adherent bacteria compared with normal control pups raised with a normal control mothers (C) [Aerobic: XFC: 7.1 ± 0.2; C: 4.5 ± 0.3; Anaerobic: XFC: 7.5 ± 0.2; C: 5.6 -+ 0.7 logl0 cfa/gm; p<0.01].In addition, XFC pups showed a significant increase in the ratio of adherent:total bacteria [XFC: 2.7 ± 0.2%; C: 0.003 ± 0.001% adherent; p<0.01] and 30% of the XFC pups had colonic neutrophilic infiltration, relative to C which had normal bacterial levels and no colonic histological injury.In contrast, IL-10 genedeficient pups cross-fostered to a normal control mother (XFKO) had reduced levels of aerobic and anaerobic colonic adherent bacteria, compared with IL-10 genedeficient pups raised with an IL-10 gene-deficient mother (KO) [Aerobic: XFKO: 5.6-+0.03;KO: 6.2-+0.2;Anaerobic: XFKO: 5.7 ±0.1; KO: 6.5-+ 0.2 log cfulgm; p<0.05] and a significantly reduced ratio of adherent:total bacteria [XFKO: 0.008 ± 0.001%; KO: 0.33 ± 0.1% adherent; p<0.01].At 4 wks of age (1 wk after weaning) the XFKO pups continued to have reduced adherent colonic bacteria and demonstrated a markedly attenuated colonic histologic injury [Histological score: 1.0 ± 0.1] relative to KO pups [Histological score: 4.8 ± 0.8; p<0.01].At 8 wk of age, 80% of XFKO pups remained free of colonic histological injury, while 100% of KO pups had severe colonic disease [Histological score = 10].Conclusions: Breast milk from IL-10 gene-deficient mice alters bacterial colonization in the intestinal lumen of pups, which leads to the development of severe colonic inflammation and ulceration.Normal breast milk from control mice fed during the critical neonatal period, confers a protective effect to IL-10 gene-deficient pups by normalizing intestinal luminal bacteria levels and thus attenuating colonic injury in later life.