Document 0474
 DOCN  M9620474
 TI    Antibodies to interleukin 12 abrogate established experimental colitis
       in mice.
 DT    9602
 AU    Neurath MF; Fuss I; Kelsall BL; Stuber E; Strober W; Mucosal Immunity
       Section, National Institutes of Health/National; Institute of Allergy
       and Infectious Diseases/LCI, Bethesda,; Maryland 20892-1890, USA.
 SO    J Exp Med. 1995 Nov 1;182(5):1281-90. Unique Identifier : AIDSLINE
       MED/96042126
 AB    In this study, we describe a novel murine model of chronic intestinal
       inflammation induced by the hapten reagent 2,4,6-trinitrobenzene
       sulfonic acid (TNBS). Rectal application of low doses of TNBS in BALB/c
       and SJL/J mice resulted in a chronic transmural colitis with severe
       diarrhea, weight loss, and rectal prolapse, an illness that mimics some
       characteristics of Crohn's disease in humans. The colon of TNBS-treated
       mice on day 7 was marked by infiltration of CD4+ T cells; furthermore,
       in situ polymerase chain reaction studies revealed high levels of
       interferon (IFN)-gamma mRNA in diseased colons. Isolated lamina propria
       (LP) CD4+ T cells from TNBS-treated mice stimulated with anti-CD3 and
       anti-CD28 antibodies exhibited a Th1 pattern of cytokine secretion: a
       20-50-fold increase in IL-2 and IFN-gamma levels and a 5-fold decrease
       in IL-4 levels as compared with those of stimulated LP CD4+ T cells from
       control BALB/c mice. Administration of monoclonal anti-IL-12 antibodies
       to the TNBS-treated mice both early (at 5 d) and late (at 20 d) after
       induction of colitis led to a striking improvement in both the clinical
       and histopathological aspects of the disease and frequently abrogated
       the established colitis completely. Furthermore, LP CD4+ T cells
       isolated from anti-IL-12-treated mice failed to secrete IFN-gamma upon
       in vitro stimulation. In summary, the data demonstrate the pivotal role
       of IL-12 and IFN-gamma in a TNBS-induced murine model of chronic
       intestinal inflammation. Furthermore, they suggest the potential utility
       of anti-IL-12 antibodies in patients with Crohn's disease.
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY/*THERAPEUTIC USE  Base
       Sequence  Colitis/CHEMICALLY INDUCED/*IMMUNOLOGY
       Colon/IMMUNOLOGY/PATHOLOGY  *Crohn Disease  CD4 Lymphocyte Count
       *Disease Models, Animal  Interferon Type II/PHYSIOLOGY
       Interleukin-12/*ANTAGONISTS & INHIB/IMMUNOLOGY/PHYSIOLOGY  Lymphocyte
       Transformation  Mice  Mice, Inbred BALB C  Mice, Inbred Strains
       Molecular Sequence Data  Spleen/IMMUNOLOGY/PATHOLOGY
       Trinitrobenzenesulfonic Acid/TOXICITY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).