Natural killer cells and tumour necrosis factor-alpha-mediated enteropathy in mice

We have shown previously that normal mice given interferon-alpha/beta (IFN-alpha/beta) or tumour necrosis factor-alpha (TNF-alpha) develop marked intestinal pathology which is similar to that found in enteropathies associated with cell-mediated immunity in vivo, such as graft-versus-host reaction (GVHR). The enteropathy induced by IFN-alpha/beta and GVHR are both dependent on the presence of natural killer (NK) cells and here we have examined whether NK cells are also required for enteropathy caused by TNF-alpha. Mice injected with recombinant TNF-alpha displayed enhanced splenic NK cell activity and developed significant villus atrophy and crypt hypertrophy in the small intestine. Administration of anti-asialo GM1 antibody abolished the NK cell activity in both normal and TNF-alpha-injected mice, but had no effect on the enteropathy caused by TNF-alpha. We conclude that NK cells are not required for TNF-alpha to damage the small intestine.