thromboxane-b2 and Crohn-Disease

Topics: Aminosalicylic Acids; Colitis, Ulcerative; Crohn Disease; Humans; Inflammatory Bowel Diseases; Leukotriene B4; Mesalamine; Prostaglandins; Sulfasalazine; Thromboxane B2

Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option.. Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease.. Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147-325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61-140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64-206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM).. Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colon; Crohn Disease; Female; Humans; In Vitro Techniques; Inflammatory Bowel Diseases; Intestinal Mucosa; Male; Middle Aged; Phthalic Acids; Rectum; Thromboxane B2

Interleukin 1 beta in biopsy specimens from inflamed colonic mucosa of patients with active inflammatory bowel disease was studied. Compared with normal colonic mucosal biopsy specimens, a significantly greater amount of interleukin 1 beta was present in rectal mucosa before (median (range) 4.3 (2.0-11.8) v 119.2 (30.1-286.8) pg/mg; p less than 0.01) and produced during organ culture (39.1 (9.4-106.8) v 97.6 (28.2-991.6) pg/mg; p less than 0.01). Values of interleukin 1 beta after culture correlated with concentrations of thromboxane B2. Organ culture of inflamed biopsy specimens in the presence of 5 aminosalicylic acid and dexamethasone reduced the amount of interleukin 1 beta detected. At the doses studied, 5 aminosalicylic acid also reduced the amount of leukotriene B4 detected after culture.

Topics: Adult; Aged; Aged, 80 and over; Aminosalicylic Acids; Colitis, Ulcerative; Colon; Crohn Disease; Dexamethasone; Female; Humans; Inflammatory Bowel Diseases; Interleukin-1; Leukotriene B4; Male; Mesalamine; Middle Aged; Organ Culture Techniques; Sulfapyridine; Thromboxane B2

Eicosanoids are modulators of defensive and inflammatory processes in the gut mucosa, and may be involved in the pathogenesis of chronic inflammatory lesions of the bowel. As omega-3 fatty acids compete with the omega-6 as precursors of eicosanoid synthesis, we compared the effects of dietary supplementation with either sunflower (source of omega-6) or cod liver (source of omega-3) oil on the development of chronic granulomatous lesions in the rat colon. After four weeks on the supplemented diets, plasma omega-6 fatty acid content was significantly higher in the sunflower group, while omega-3 fatty acids predominated in the cod liver group. Inflammatory colitis was then induced by intracolonic administration of trinitrobenzene sulphonic acid. Luminal eicosanoid release, as measured by radioimmunoassay of intracolonic dialysis fluid, increased significantly after the challenge in both groups. Generation of prostaglandin E2 (PGE2) and leucotriene B4 (LTB4) peaked by day 3 and thereafter declined; thromboxane B2 (TXB2), instead, continued to increase from day 3 to 20 in sunflower fed rats, whereas this change was blunted in cod liver animals. The rats were killed 20, 30, or 50 days after the induction of colitis, and the colonic lesions were scored macroscopically (adhesions to surrounding tissues, strictures, ulcerations, and wall thickness) and histologically (ulceration, inflammation, depth of the lesions, and fibrosis). In cod liver animals, the damage score was markedly reduced by day 30, and inflammation and ulceration were almost absent by day 50. In conclusion, a fish oil diet prevents the increase in thromboxane in the chronic state of inflammation and shortens the course of the colonic disease by diminishing both the severity of the lesions and their progression to chronicity.

Topics: Animals; Body Weight; Cod Liver Oil; Crohn Disease; Dietary Fats; Dinoprostone; Fatty Acids; Fatty Acids, Omega-3; Fish Oils; Helianthus; Leukotriene B4; Male; Plant Oils; Rats; Rats, Inbred Strains; Thromboxane B2; Trinitrobenzenesulfonic Acid

To compare the local release of arachidonic acid metabolites in inflammatory diarrheal disease, in vivo equilibrium dialysis of the rectum was done in consecutive untreated patients with ulcerative colitis (n = 20), Crohn's colitis (n = 10), and Clostridium difficile colitis (n = 7). All patients had endoscopically proven rectal inflammation. Eicosanoid profiles were determined in rectal dialysates by radioimmunoassay after preliminary purification. Concentrations of prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2, but not 6-keto-prostaglandin F1 alpha, were raised in all groups and compared with healthy controls. The highest levels within each group were obtained in patients with widespread epithelial damage, as judged by endoscopy. In patients with ulcerative colitis, an extreme rise in prostaglandin E2 and thromboxane B2 were observed. Similarly, concentrations of leukotriene B4 were substantially increased in ulcerative colitis, but in Crohn's colitis and Clostridium difficile colitis only those patients with rectal ulcerations showed elevations. These findings probably reflect more severe tissue damages in ulcerative colitis, but differences between disease groups in cell-to-cell interaction may also contribute. The data suggest, therefore, that therapeutic inhibition of lipoxygenase pathways may prove more effective in ulcerative colitis than in Crohn's disease.

Topics: Adolescent; Adult; Aged; Arachidonic Acid; Arachidonic Acids; Colitis; Colitis, Ulcerative; Crohn Disease; Dialysis; Dinoprost; Dinoprostone; Eicosanoic Acids; Enterocolitis, Pseudomembranous; Female; Humans; Leukotriene B4; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Rectum; Thromboxane B2

Prostanoids are important for the pathogenesis of chronic inflammatory bowel diseases as mediators of inflammatory, immune and allergic reactions. The levels of thromboxane B2(TXB2), the stable hydrolysis product of thromboxane A2(TXA2) were determined in blood plasma of patients with chronic inflammatory bowel diseases. The platelet malondialdehyde (MDA) formation was determined as an indicator of the TXA2 synthetase activity. The TXB2 concentrations were measured radioimmunologically. The platelet MDA formation induced by N-ethylmaleimide was investigated with the thiobarbituric acid reaction. The investigated patients (n = 10) suffering from ulcerative colitis had a significant increasing (p less than 0.02) of the platelet MDA formation (mean = 4.39 nmol/10(9) platelets) in comparison to the normal group (n = 20; mean = 2.87; nmol/10(9) platelets). The increasing of TXB2 levels was not significantly different than in normal control subjects. The plasma concentrations of 6-keto-PGF1 were situated on the limit of detection.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Colitis, Ulcerative; Crohn Disease; Humans; Middle Aged; Recurrence; Thromboxane A2; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acids; Colitis, Ulcerative; Crohn Disease; Dinoprostone; Female; Humans; Intestinal Mucosa; Male; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Thromboxane B2

Synthesis of prostanoids in Crohn's disease was investigated using rectal biopsy specimens maintained in organ culture. As with ulcerative colitis increased synthesis of prostaglandin (PG)E2 was observed when the mucosa was inflamed, compared with uninflamed mucosa in Crohn's disease, and with control biopsy specimens. In contrast with ulcerative colitis differences from control specimens were observed even in the absence of inflammation. There was a raised synthesis of thromboxane (Tx)B2 (stable breakdown product of TxA2); concentrations of 6-keto PGF1 alpha (stable breakdown product of prostacyclin) were unchanged and hence the ratio of 6-keto PGF1 alpha/TxB2 was reduced. These changes might lead to an altered cytoprotective capacity or reduced suppressor cell activity, such as has previously been reported in intestinal lymphocytes in Crohn's disease.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Crohn Disease; Dinoprostone; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Organ Culture Techniques; Prostaglandins E; Rectum; Thromboxane B2; Thromboxanes

Prostanoid synthesis by cultured peripheral blood mononuclear cells and monocytes in inflammatory bowel disease patients was determined because monocytosis was reported in inflammatory bowel diseases and prostanoids are synthesized by peripheral blood mononuclear cells in response to inflammatory stimuli. Prostaglandin E2 and thromboxane B2 accumulation in the medium of cultured peripheral blood mononuclear cells isolated from patients with active Crohn's disease was two and three times higher than their respective accumulation by peripheral blood mononuclear cells isolated from normal subjects or patients in remission. In ulcerative colitis, prostaglandin E2 and thromboxane B2 accumulation was not enhanced. 6-Keto-prostaglandin F1 alpha was not detected in any of the cultured medium. The absolute number of monocytes was determined according to their adherence to plastic surfaces, and the percent of phagocytic cells was significantly higher among peripheral blood mononuclear cells in patients with Crohn's disease and ulcerative colitis as compared with peripheral blood mononuclear cells isolated from normal subjects. However, prostaglandin E2 secretion, by the same number of cultured monocytes isolated from all groups of patients, was similar. Flufenamic acid, methylprednisolone, and 5-aminosalicylic acid significantly inhibited prostaglandin E2 and thromboxane B2 accumulation. These results suggest that in Crohn's disease enhanced prostanoid synthesis is probably due to the monocytosis, whereas in ulcerative colitis the monocytosis is not accompanied by a significant increase in prostanoid synthesis in vitro.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Cells, Cultured; Colitis, Ulcerative; Crohn Disease; Dinoprostone; Female; Humans; Male; Middle Aged; Monocytes; Prostaglandins E; Thromboxane B2; Thromboxanes