A ROLE FOR INTERLEUKIN-1-ALPHA IN IMMUNOLOGICALLY MEDIATED INTESTINALPATHOLOGY

Interleukin-1 (IL-1) is an important mediator of inflammation and has been implicated in several forms of immunopathology. Here we have inve stigated whether IL-1 plays a role in the enteropathy which occurs dur ing a graft-versus-host reaction (GVHR) in mice. Non-irradiated (CBA x BALB/c) F1 mice with GVHR had increased production of IL-1 and treatm ent with rabbit anti-IL-1alpha antibodies abolished the crypt hyperpla sia and significantly reduced the parallel increase in crypt length wh ich occurs in the jejunum. Antibody treatment had no effect on the acc ompanying increase in intraepithelial lymphocyte (IEL) counts or on th e splenomegaly. Recombinant IL-1 itself produced villus atrophy, crypt hyperplasia and increased IEL counts in normal mice and stimulated th e proliferation of an intestinal epithelial cell line in vitro. We pro pose that IL-1 plays an effector role in immunologically mediated ente ropathy, either via direct effects on epithelial cells or secondary to an action on other, stromal cells in the mucosa.