Inhibition of platelet activation by 5-aminosalicylic acid in inflammatory bowel disease.
BACKGROUND
Platelets play an important role in inflammation and are activated in inflammatory bowel disease. Micro-vascular thrombosis in the gut wall leading to intestinal micro-infarction may be a pathogenic feature of Crohn's disease. 5-Aminosalicylic acid is an effective treatment for patients with inflammatory bowel disease.


OBJECTIVE
To assess the effects of 5-aminosalicylic acid on platelet activation, when taken orally and in vitro by patients with inflammatory bowel disease.


METHODS
Spontaneous and thrombin-induced platelet activation were studied using fluorescent antibodies to the activated platelet surface glycoprotein P-selectin and flow cytometry.


RESULTS
Baseline platelet activation in inflammatory bowel disease was significantly greater than that in controls (P=0.0003). Independent of diagnosis or disease activity, spontaneous ex-vivo platelet activation was 50% lower in patients with inflammatory bowel disease taking 5-aminosalicylic acid orally than in those not on such treatment (P < 0.05). In vitro, 5-aminosalicylic acid significantly reduced both spontaneous (P < 0. 03 for >/=1 microM 5-aminosalicylic acid) and thrombin-induced platelet activation (P < 0.02 for >/= 1 microM 5-aminosalicylic acid).


CONCLUSIONS
5-Aminosalicylic acid given either orally or in vitro inhibits platelet activation. If this effect reflects an in vivo action in the gut, it could contribute to the beneficial actions of 5-aminosalicylic acid in inflammatory bowel disease.
Carty
E
E
Digestive Diseases Research Centre, St Bartholomew's & The Royal London School of Medicine and Dentistry, London, UK. e.carty@mds.qmw.ac.uk
MacEy
M
M
Rampton
D S
DS
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019007:P-Selectin; D019804:Mesalamine