Nitric oxide mediates intestinal pathology in graft‐vs.‐host disease

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Abstract
We have investigated the involvement of nitric oxide (NO) in intestinal graft‐vs.‐host reaction (GvHR) in mice. Treatment of mice with L‐NG‐monomethyl arginine (L‐NMMA), a specific inhibitor of NO synthesis, abolished the mucosal pathology of intestinal GvHR and reduced the associated lymphocytic infiltration of the epithelium. L‐NMMA had no effect on splenomegaly in GvHR, nor did it interfere with the growth of an undifferentiated crypt stem cell line, or the production of tumor necrosis factor‐α by activated macrophages in vitro. In contrast, L‐NMMA inhibited the enhanced activity of natural killer (NK) cells which occurs in GvHR. We conclude that a NO‐dependent mechanism is essential for intestinal immunopathology in GvHR and that this may reflect a role for NO in NK cell function.