Analysis of enteropathy induced by tumour necrosis factor alpha.
Tumour necrosis factor (TNF)-alpha has been implicated in the pathogenesis of experimental and clinical enteropathy, but its exact role is unknown. We show here that a single dose of TNF-alpha causes significant small intestinal pathology in normal adult mice, which develops within 15 minutes, persists for up to 48 hours and is enhanced by interferon-gamma (IFN-gamma). The enteropathy consists of villus atrophy and crypt hyperplasia and is therefore similar to that found in immunologically mediated enteropathies such as graft-versus-host reaction (GvHR). TNF-alpha is also cytotoxic to an intestinal crypt cell line in vitro. Thus, a direct action of TNF-alpha on crypt cells may be involved in its enteropathic effects in vivo. Together, these findings indicate that TNF-alpha alone, or in concert with other cytokines, may be an important effector molecule in immunologically mediated intestinal pathology and may ultimately provide a target for specific immunotherapy for clinical enteropathies.
Garside
P
P
Department of Immunology, University of Glasgow, Western Infirmary.
Bunce
C
C
Tomlinson
R C
RC
Nichols
B L
BL
Mowat
A M
AM
D000818:Animals; D002460:Cell Line; D004357:Drug Synergism; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D007371:Interferon-gamma / Q000633:toxicity; D007410:Intestinal Diseases / Q000139:chemically induced*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000648:ultrastructure; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma