Below are reports on three presentations.
They said that experimental models have shown that blockade of VLA-4, VCAM-1 and P-selectin afford significant amelioration of intestinal inflammation. In experimental models, response to adhesion molecule blockage varies according to the type of inflammatory intestinal condition. In humans VLA-4 immunoneutralization has been effective in inducing remission in Crohn's Disease, but no data is available for ulcerative colitis.
The researchers call for experimental and clinical controlled trials comparing the effectiveness of different strategies of CAM blockade, and suggest that this therapeutic approach be compared with current therapies.
Researchers from LSU and the University of Muenster studied the mechanisms responsible for platelet-WBC and platelet-endothelial cell (EC) interactions that occur in experimental colitis. This was prompted by the recognition of cross-talk between platelets and leukocytes in inflammation. Compared with controls, colitis-induced wild type mice showed significantly increased adhesion of platelets, with 2.5% of platelets adhering to ECs directly and 97.5% binding to adherent WBC. ICAM-1 deficient mice with induced colitis had significantly decreased platelet-WBC adhesion.
Wild-type mice made neutropenic with anti-netrophil serum (ANS) exhibited reduced platelet-WBC binding, but significantly increased platelet-EC adhesion. The increase in platelet-EC adhesion in neutropenic animals was presented by both, a single dose of either P-selectin of PSGL-1 blocking monoclonal antibody.
They conclude that in induced colitis, platelet accumulation in venules is dependent on both leukocyte adhesion as well as on mechanisms involving the adhesion molecules P-selectin and PSGL-1. The researchers from the Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, include Thorsten Vowinkel, Mikiji Mori, Katherine Wood, Janice Russel and D. Neil Granger; and Christian F. Krieglstein from the Department of General Surgery, University of Muenster, Germany.
Researchers at the Division of Gastroenterology of Washington University School of Medicine, St. Louis, Mo., wanted to determine if the biological agent CTLA-4-Ig would abrogate trinitrobenzene sulfonic acid (TNBS) colitis, and if so, to determine if indoleamine 2,3-dioxygenase (IDO) played a role in the process.
The researchers included Gregory J. Gurtner, Thomas M. Ogel, Suzanne R. Schloemann, Keely G. McDonald, Rodney D. Newberry and William F. Stenson.
They found that CTLA-4-Ig induced IDO in the murine colon after systemic administration.
Intraperitonial CTLA-4-Ig administration prior to TNBS administration significantly abrogated colitis both clinically and by histological criteria. Mice treated with CTLA-4-Ig and TNBS had a 100% survival rate and a significant reduction in colonic TNFámRNA expression regardless of IDO inhibition. IDO inhibition with 1-methyl-tryptophan (1mT), however, prevented colitis abrogation by CTLA-4-Ig both clinically and by histological criteria, and decreased colonic TGFâmRNA expression.
The researchers conclude their study suggests that CTLA-4-Ig promotes tolerance in TNBS colitis both via IDO induction as well as through costimulatory blockade, and suggests a potential therapeutic role for CTLA-4-Ig in treating IBD.
The APS conference, "Immunological and Pathophysiological Mechanisms in Inflammatory Bowel Diseases" was also supported by Centocor Inc., Hoffman-La Roche Inc., the National Institutes of Health-NIDDK, and the Crohn's and Colitis Foundation of America.
For a complete list of the speakers and topics at the conference please go to: http://www.the-aps.org/press/conference/ibd04conf.htm
Other press releases from the conference can be found at: http://www.the-aps.org/press/conference/
Editor's note: Telephone or in-person media interviews can be arranged with any of the speakers by contacting Mayer Resnick at APS headquarters -- 301-634-7209 (office), 301-332-4402 (cell) or mresnick@the-aps.org -- during or after the conference.
APS contact
Mayer Resnick
301-634-7209
301-332-4402 (cell)
mresnick@the-aps.org
Next meeting
APS Intersociety Meeting on the INTEGRATIVE BIOLOGY OF EXERCISE
Co-sponsored by the American Physiological Society,
Canadian Society for Exercise Physiology and the
American College of Sports Medicine
Oct. 6-9, 2004, Austin, Texas
http://www.the-aps.org/meetings/aps/austin/index.htm
The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has more than 10,000 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.
APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In May, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM).