From inflammation to lesion.

Abstract

The gastrointestinal tract is continuously in contact with a multitude of antigens and therefore contains a well developed defense mechanism composed of nonspecific and specific elements. The gastrointestinal mucosa immune system (GALT) is the specific defense. Its cellular components firstly appear during the 11th week of pregnancy. Stimulation of the lymphoid tissue starts early after birth and depends upon bacterial colonization. During life the immune system is continuously bombarded by a multitude of antigens. The normal presence of the GALT is the expression of a controlled physiologic inflammation. Inflammation is a complex series of homeostatic reactions involving cellular and molecular mechanisms orchestrated in such a manner as to protect the organism, only yielding pathologic changes when there is overwhelming acute response or when chronicity leads to loss of function. Several phases can be distinguished in the inflammatory reaction. The initial vascular reaction, controlled by vasoactive mediators is followed by a cellular reaction with recruitment of inflammatory cells (immune competent leucocytes and neutrophils). This process requires cellular adhesion and migration and depends on the expression of "adhesion molecules". Leucocytes already present in the tissue (lymphocytes monocyte/macrophage cells, eosinophils, and mast cells) and newly recruited cells (neutrophils, eosinophils, monocyte/macrophage cells and lymphocytes) will release a variety of inflammatory mediators with both positive and negative (tissue destructive) effects. Epithelial cells, fibroblasts and smooth muscle cells are actively involved in the reaction. Normally inflammation ends by healing. In chronic inflammatory bowel diseases healing does not occur or is incomplete. Early lesions described thus far for the small capillary lesions described in Crohn's disease). Yet similar lesions not leading to chronicity have been described in experimental and human clinical conditions. The major question therefore in Crohn's disease and ulcerative colitis is why the early lesions do not heal but lead to chronic inflammation. Intrinsic defects (alterations of epithelial cells, increased permeability or genetic predisposition) are considered as possible causes. Persistent inflammation may also be due to the nature of an extrinsic agent as in tuberculosis. A specific agent has as yet not been demonstrated in chronic idiopathic inflammatory bowel disease. An inappropriate inflammatory reaction to components normally present in the lumen of the gastrointestinal tract must also be considered. Heat shock proteins (HSP) produced by bacterial agents may for instance induce an autoimmune reaction as there is molecular analogy between HSP from bacterial origin and human HSP.