Interleukin-12 antagonists as new therapeutic agents in inflammatory bowel disease.
Inflammatory bowel diseases (IBDs; Crohn's disease (CD) and ulcerative colitis) are chronic inflammatory diseases leading to destruction of gastrointestinal tissue. They are characterized by an exaggerated immune response. In CD, an increased expression of T-helper-1 (Th1) cytokines was observed in which interleukin-12 (IL-12) seems to play a pivotal role. Different immunosuppressive agents have been used to treat patients suffering from IBD, nevertheless remarkable side effects or treatment failure are limiting factors in this regard. Therefore, studies on more specific treatment of CD have recently been published, using recombinant anti-inflammatory cytokines or inhibitors of proinflammatory cytokines and their receptors. Beyond these principles anti-IL-12 strategies seem to play a promising role because of the central position of this Th1-inducing cytokine in the inflammatory cascade. Up to now anti-IL-12 antibodies, complement receptor-3 antibodies and IL-12p40 homodimers have been evaluated in their potential to suppress the mucosal inflammation. Based on our understanding of the pathogenesis of CD, the available data and experiences concerning these principles are presented in this review.
Schmidt
Carsten
C
Abteilung für Innere Medizin II, Universität des Saarlandes, Homburg/Saar, Deutschland.
Marth
Thomas
T
Wittig
Bianca M
BM
Hombach
Andreas
A
Abken
Hinrich
H
Stallmach
Andreas
A
D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000276:immunology / Q000628:therapy*; D003424:Crohn Disease / Q000276:immunology / Q000628:therapy*; D019281:Dimerization; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D053762:Interleukin-12 Subunit p40; D016177:Macrophage-1 Antigen / Q000276:immunology*; D051379:Mice; D021122:Protein Subunits / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D019138:Antibodies, Blocking; D000922:Immunotoxins; D053762:Interleukin-12 Subunit p40; D016177:Macrophage-1 Antigen; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D018664:Interleukin-12