INCREASED TRANSLOCATION OF ESCHERICHIA-COLI AND DEVELOPMENT OF ARTHRITIS IN VITAMIN-A-DEFICIENT RATS

We studied the immune response and the colonization pattern in vitamin A-deficient rats that were colonized with the Escherichia coli O6 K13 pOmp 21 strain, which is genetically manipulated to produce ovalbumin and to be resistant to ampicillin, In the vitamin A-deficient rats, t he number of bacteria per gram of feces was about five times higher th an in the paired fed control rats 4 weeks after colonization. In the c ontrol rats, the colon and the lower part of the ileum were colonized, while in the vitamin A deficient rats ah parts of the small intestine , as well as the colon, were heavily inhabited by bacteria. Furthermor e, in 75% of the vitamin A-deficient rats, the E. coli bacteria were f ound in the mesenteric lymph nodes, and in 50% of the rats E. coli wer e found in the kidneys. These animals also developed severe arthritis. The levels of serum immunoglobulin G (IgG), IgM, IgE, and biliary IgA antibodies against the bacterial antigens were significantly higher i n the vitamin A deficient rats than in the control rats. The number of IgA-producing cells in the lamina propria of the small intestine was significantly lower in the vitamin A-deficient rats than in the contro l rats; however, there was an increase in the number of CD8(+) cells a nd transforming growth factor beta-producing cells in the lamina propr ia of the vitamin A-deficient rats. Disturbances in T-cell function we re demonstrated, since spleen cells ti om the vitamin A-deficient rats produced more gamma interferon and interleukin-2 in vitro than contro l spleen cells. In summary, vitamin A deficiency led to a decrease in the ability to control the localization of intestinal bacteria and an increase in translocation, which was followed by development of arthri tis regardless of substantial levels of antibacterial antibodies. The bacterial invasion made the animals hyperresponsive to the bacterial a ntigens, despite the fact that vitamin A deficiency is normally associ ated with suppressed antibody production, as previously shown by us an d others.