Observations on the role of endotoxin in graft-versus-host disease.

We have used a conventional murine model of bone marrow transplantation (BMT) to make a detailed study of the histological features of graft-versus-host disease (GvHD), and to study the effects of oral antibiotic decontamination of the gut flora. Comparison of the histological appearances of the small and large bowel indicated that the features of the GvHD were more severe in the large bowel. Bowel sterilisation caused a striking reduction in the severity of GvHD, both in the gut and at a distant site (the skin of the ear). The different effects of GvHD in the large as compared to the small bowel suggested that a factor was operative locally, and the effect of sterilisation linked this to the bacteria in the bowel. The fact that sites remote from the bowel were also affected suggested that a diffusible factor from the bowel produced by the bacteria of the gut was responsible. Studies elsewhere have suggested that the factor involved is likely to be endotoxin. In these experiments however it was evident that systemic administration of endotoxin did not aggravate the disease process and that in some instances the reverse was obtained. If therefore endotoxin is important the dose and its mode of its administration are likely to be critical.