Extended Abstracts of the Lectures: THURSDAY, NOVEMBER 23, 2006 OPENING LECTURES
Background: Aluminum (AL) is a common environmental compound with immune adjuvant activity and granulomatous inflammation inducer. AL exposure in food additives, air and water pollution is ubiquitous in western cultures. Since loss of tolerance to commensal intestinal bacteria is involved in the pathogenesis of IBD, we postulate that dietary AL increases luminal bacterial virulence and/or enhances mucosal immune responses to enteric bacteria. Therefore, AL effects on bacterial growth, the ability of intestinal bacterial lysate to stimulate effector immune responses, the capacity of AL preloaded pathogenic bacteria to enhance immune responses in vitro and the in vivo effect of dietary AL on immune- mediated young murine colitis, were explored.
Methods: Growth of murine intestinal bacterial on increasing AL concentration (AL 0-662 μM) was assessed by spectrophotometry. Immune responses were studied by
[H]3 Thymidine incorporation, gamma-interferon by Elisa on IL-10 KO colitic mouse splenocytes stimulated by murine E. coli grown in increasing AL concentrations. Young 15 IL-10 KO germ free mice were colonized with specific pathogen free enteric microbiota, fed a low AL, and exposed to 3 different AL concentrations: low (0.03 μM), middle (5 μM) and high (500 μM) AL L-lactate added to their drinking water. Colitis was measured by blinded histologic scores (0-4+) and spontaneous IL-12 secretion by cultured colonic fragments.
Results: Bacterial growth was suppressed slightly by high AL concentrations in the media. Lower AL concentrations (150-200 μM) stimulated, while higher concentrations inhibited in vitro T cell proliferation and IFN secretion by splenocytes. In vivo AL feeding worsened colitis, with increased cecal histological scores accompanying higher AL intake (2.0 ± 0.2 low vs. 3.8 ± 0.2 high, p<0.05). Colonic IL-12 secretion by colonic strip cultures increased with higher AL intake (3.5 ± 1.6 vs. 4.9 ± 0.4 ng/ml). Dietary AL affected luminal bacterial metabolism by inducing pink E. coli colonies on MacConkey agar plates.
Conclusions: Environmental AL stimulates immune responses to enteric bacteria in vitro and enhances bacterial- induced experimental colitis in Young IL-10 KO mice. Dietary exposure to AL may in part explain the increased incidence of pediatric IBD in Western countries adopting Western culture.