Role of platelet-activating factor in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine and prednisolone.
Platelet-activating factor is released from inflammatory cells. It activates neutrophils, releases secondary messengers, and mediates mucosal ulceration and ischemia in the rat. We assessed its possible role in the pathogenesis of ulcerative colitis. Colonic biopsy specimens from patients with active ulcerative colitis and controls were incubated for 4 h in Tyrode's buffer in the presence or absence of 0.2 microM calcium ionophore (A23187) or 50 microliter of antihuman immunoglobulin E. Platelet-activating factor was determined in the tissue by aggregation assay after extraction with 80% ethanol and was confirmed by thin-layer chromatography and its inactivation by phospholipases. Platelet-activating factor was not detected in normal mucosa. Only A23187 and antihuman immunoglobulin E stimulated its activity: mean +/- SE, 43.2 +/- 8.6 and 33.0 +/- 6.1 pg/10 mg wet wt, respectively. In active ulcerative colitis basal platelet-activating factor activity was 8.9 +/- 3.5 pg/10 mg wet wt. A23187 and antihuman immunoglobulin E induced significantly higher stimulation of platelet-activating factor synthesis when compared with their effects on normal mucosa: 200 +/- 28 and 70 +/- 8.3 pg/10 mg wet wt, respectively. The enhanced stimulation induced by A23187 was dose-dependently inhibited by salazopyrine, 5-amino-salicylic acid, and prednisolone, but not by sulfapyridine. It is thus suggested that platelet-activating factor may be involved in the pathogenesis of the inflammatory response in ulcerative colitis and that its inhibition by steroids, 5-aminosalicylic acid, and salazopyrine may be an additional mechanism to explain their therapeutic effects.
D000328:Adult; D000636:Aminosalicylic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000209:etiology / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D004338:Drug Combinations / Q000494:pharmacology; D005260:Female; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D011239:Prednisolone / Q000494:pharmacology*; D012007:Rectum / Q000378:metabolism; D013427:Sulfapyridine / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D004338:Drug Combinations; D010972:Platelet Activating Factor; C028423:Salazopyrine; D007073:Immunoglobulin E; D000001:Calcimycin; D012460:Sulfasalazine; D011239:Prednisolone; D005944:Glucosamine; D013427:Sulfapyridine