HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

A CD3-specific antibody reduces cytokine production and alters phosphoprotein profiles in intestinal tissues from patients with inflammatory bowel disease.

AbstractBACKGROUND & AIMS:
T cells mediate the development of inflammation in inflammatory bowel disease (IBD). We investigated the effects of an antibody against CD3 called otelixizumab, which induces immune tolerance, in intestinal mucosa samples from patients.
METHODS:
Intestinal tissues were isolated from patients undergoing routine endoscopy or from patients undergoing intestinal surgery for colon cancer or IBD; healthy surrounding tissues were collected as controls. Isolated lamina propria mononuclear cells (LPMCs) and mucosal tissue explants were incubated with otelixizumab for 24 or 48 hours. Production of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. Levels of 36 cytokines and chemokines and phosphorylation of 39 receptor tyrosine kinases and signaling molecules were measured using protein arrays. Immunoblot analysis was used to analyze T-cell transcription factors.
RESULTS:
Incubation of intestinal tissues or LPMCs with otelixizumab reduced production of interferon gamma, interleukin (IL)-17A, and other inflammatory cytokines and chemokines, simultaneously increasing production of IL-10. Mucosal biopsy specimens from patients with IBD retained inflammation-associated tyrosine phosphoprotein profiles ex vivo. Incubation of the inflamed tissue with otelixizumab reduced phosphorylation of these proteins to levels observed in control tissues. Otelixizumab also markedly reduced phosphorylation of proteins associated with T-cell receptor activation. Neutralization of IL-10 blocked the anti-inflammatory effects of otelixizumab.
CONCLUSIONS:
We observed anti-inflammatory effects of anti-CD3 in inflamed intestinal tissues from patients with IBD. The antibody appears to down-regulate T-cell activation via IL-10.
AuthorsAnna Vossenkämper, Christian Hundsrucker, Kevin Page, André van Maurik, Theodore J Sanders, Andrew J Stagg, Lisa Das, Thomas T MacDonald
JournalGastroenterology (Gastroenterology) Vol. 147 Issue 1 Pg. 172-83 (Jul 2014) ISSN: 1528-0012 [Electronic] United States
PMID24704524 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • CD3 Complex
  • Cytokines
  • Interleukin-17
  • Phosphoproteins
  • Interleukin-10
  • Interferon-gamma
  • otelixizumab
Topics
  • Adolescent
  • Adult
  • Antibodies, Monoclonal (pharmacology)
  • Antibodies, Monoclonal, Humanized (pharmacology)
  • Biopsy
  • CD3 Complex (immunology)
  • Case-Control Studies
  • Colon (drug effects, metabolism, pathology)
  • Cytokines (metabolism)
  • Female
  • Humans
  • Immune Tolerance (drug effects)
  • Inflammatory Bowel Diseases (metabolism, pathology)
  • Interferon-gamma (metabolism)
  • Interleukin-10 (metabolism)
  • Interleukin-17 (metabolism)
  • Intestinal Mucosa (drug effects, metabolism, pathology)
  • Male
  • Middle Aged
  • Phosphoproteins (metabolism)
  • Young Adult

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: