PMID- 9027661
OWN - NLM
STAT- MEDLINE
DCOM- 19970529
LR  - 20190920
IS  - 0944-1174 (Print)
IS  - 0944-1174 (Linking)
VI  - 31
IP  - 6
DP  - 1996 Dec
TI  - Alterations of the mucosal immune system in inflammatory bowel disease.
PG  - 907-16
AB  - The normal intestinal immune system is under a balance in which proinflammatory 
      and anti-inflammatory cells and molecules are carefully regulated to promote a 
      normal host mucosal defense capability without destruction of intestinal tissue. 
      Once this careful regulatory balance is disturbed, nonspecific stimulation and 
      activation can lead to increased amounts of potent destructive immunologica and 
      inflammatory molecules being produced and released. The concept of balance and 
      regulation of normal mucosal immune and inflammatory events is indicative of how 
      close the intestine is to developing severe inflammation. The normal intestinal 
      mucosal immune system is constantly stimulated by lumenal contents and bacteria. 
      The stimulatory molecules present in the intestinal lumen that activate and 
      induce subsequent mucosal immunologic and inflammatory events include bacterial 
      cell wall products, such as peptidoglycans and lipopolysaccharides, as well as 
      other chemotactic and toxic bacterial products that are produced by the many 
      different types of bacteria within the gastrointestinal tract. These highly 
      stimulatory bacterial cell wall products are capable of activating macrophages 
      and T lymphocytes to release potent proinflammatory cytokines, including 
      interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha 
      (TNF-alpha). IL-1, IL-6, and TNF-alpha increase the presence of human leukocyte 
      antigen (HLA) class II antigen-presenting molecules on the surfaces of epithelial 
      cells, endothelial cells, macrophages, and B cells, thus increasing their ability 
      to present lumenal antigens and bacterial products. The proinflammatory cytokines 
      IL-1 and TNF-alpha also increase the ability of epithelial cells, endothelial 
      cells, macrophages, and fibroblasts to secrete potent chemotactic cytokines, such 
      as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), which 
      serve to increase the movement of macrophages and granulocytes from the 
      circulation into the inflamed mucosa. Thus, through lumenal exposure to potent, 
      nonspecific stimulatory bacterial products, the state of activation of the 
      intestinal immune system and mucosal inflammatory pathways are markedly 
      up-regulated. This raises the question of whether there is a deficiency in 
      effective down-regulation through the absence of normally suppressive cytokines 
      such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), 
      interleukin-4 (IL-4), and IL-1 receptor antagonist. Normally, the turning off of 
      the active and destructive immunologic and inflammatory events should occur 
      following the resolution of a bacterial or viral infection that has been 
      appropriately defended against and controlled by the mucosal immune system. In 
      inflammatory bowel disease (IBD), however, the down-regulatory events and 
      processes that should turn off the immunologic and inflammatory protective 
      processes, once the pathogenic agent has been cleared, appear to be deficient or 
      only partially effective. We may find that we ultimately are dealing with disease 
      processes that have more than one genetic or cellular basis. The improved 
      understanding of the immunopathophysiology of IBD will allow exploration of novel 
      immunologic and genetic approaches, such as gene replacement therapy, 
      administration of a suppressor cytokine or an altered cell surface antigen, the 
      administration of humanized monoclonal antibodies directed against 
      proinflammatory cytokines, or the development of newer strategies against 
      fundamental cell biologic mechanisms such as adhesion molecules.
FAU - MacDermott, R P
AU  - MacDermott RP
AD  - Gastroenterology Section, Lahey Hitchcock Medical Center, Burlington, MA 01805, 
      USA.
LA  - eng
GR  - DK 21474/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulins)
SB  - IM
MH  - Animals
MH  - Cytokines/biosynthesis/immunology
MH  - Granulocytes/immunology/metabolism
MH  - Humans
MH  - Immunoglobulins/biosynthesis/immunology
MH  - Inflammatory Bowel Diseases/*immunology/metabolism/pathology
MH  - Intestinal Mucosa/*immunology/metabolism/pathology
MH  - T-Lymphocytes/immunology/metabolism
RF  - 84
EDAT- 1996/12/01 00:00
MHDA- 1996/12/01 00:01
CRDT- 1996/12/01 00:00
PHST- 1996/12/01 00:00 [pubmed]
PHST- 1996/12/01 00:01 [medline]
PHST- 1996/12/01 00:00 [entrez]
AID - 10.1007/BF02358624 [doi]
PST - ppublish
SO  - J Gastroenterol. 1996 Dec;31(6):907-16. doi: 10.1007/BF02358624.