VITAMIN-A-DEFICIENCY EXACERBATES MURINE LYME ARTHRITIS

Vitamin A deficiency predisposes the host for a strong inflammatory re sponse, suggesting that it may foster susceptibility to diseases, such as Lyme arthritis, in which activated macrophage and inflammatory cyt okine production are pathogenic. Infected mice had a rapid serum retin ol decline that correlated with the onset of arthritis. The mice with the least retinol developed acute arthritis earlier and more severely than those with the highest retinol. Earlier and stronger interleukin (IL)-12, interferon-gamma (IFN)-gamma, and tumor necrosis factor respo nses were found in Borrelia burgdolferi-infected, vitamin A-deficient mice compared with controls. The spirochetes induced IFN-gamma secreti on from unprimed cells, and retinoid addition in vitro inhibited IFN-g amma synthesis. Vitamin A deficiency may exacerbate acute Lyme arthrit is by enhancing an acute arthritogenic inflammatory response initiated by spirochete-driven IFN-gamma secretion. Conversely, vitamin A may l essen acute Lyme arthritis pathology by blocking IFN-gamma and IL-12 s ynthesis.