Influence of sulphasalazine and mesalazine on cellular and biochemical oxygen metabolite production. Effect of in vivo administration and an in vitro analysis.

Oxidative damage has been implicated in the pathogenesis of inflammatory bowel disease. In the present study sulphasalazine and mesalazine (5-aminosalicylic acid) in vitro were shown to possess scavenging activity and to attenuate the production of oxygen metabolites by neutrophils. In a double-blind randomized crossover study, with five patients with inflammatory bowel disease in remission and four healthy controls, we evaluated the influence of in vivo administration of sulphasalazine and mesalazine on the neutrophil oxygen metabolite production in vitro. Apart from a small but significant increase in the neutrophil H2O2 and O2 production by sulphasalazine, in particular in controls, in vivo administration of both drugs hardly affected the oxygen metabolite-producing capacity of the cells. This observation was confirmed by in vitro preincubation of neutrophils with the drugs and subsequent oxygen metabolite production analysis. It is concluded that sulphasalazine and mesalazine do not influence the oxidative capacity of neutrophils, but scavenge and attenuate the production of oxygen metabolites when present in the immediate surroundings of the cells. Thus, protection against oxidative damage is definitely one of the modes of action of these drugs.

Inhibition of cell mediated cytotoxicity by sulphasalazine: effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural killer cell activity.

Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel disease, particularly in patients with active disease. It is not clear, however, whether this decrease is caused by the disease or is a consequence of the medical treatment. In this study we evaluated the effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on the in vitro natural killer cell activity in five patients with inflammatory bowel disease in remission and in four healthy control subjects in a double blind randomised crossover trial preceded and separated by four weeks of treatment with placebo. The natural killer cell activity was significantly impaired in 67% (six of nine subjects) after four weeks' sulphasalazine treatment and tended to be related to subjects with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment caused only a marginal reaction in the natural killer cell activity in 22% (two of nine subjects). The inhibitory effects were found to be reversible since the decreased natural killer cell activity was completely restored after placebo treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety. This phenomenon may contribute to the low natural killer cell activity found in patients with active inflammatory bowel disease.

Value of indium-111 tropolonate autologous granulocyte scintigraphy in the assessment of inflammatory bowel disease.

Indium-111 autologous leucocyte scanning is a non-invasive and reliable technique for the detection of abdominal abscesses. In the past decade several papers have been published concerning the use of this technique in the assessment of inflammatory bowel disease (IBD) with variable results. We conducted a prospective study of 62 patients with IBD attending the Leiden University Hospital, to assess the diagnostic value of indium-111 tropolonate autologous granulocyte scanning. Fifty-one patients had Crohn's disease (CD) (30 with involvement of the small bowel, 18 the colon only, and 3 patients had both localizations), and 11 had ulcerative colitis (UC). Twenty-one of 26 patients with evidence of active disease of the small intestine had a true-positive scan (sensitivity, 80%). However, accurate assessment of localization and extent of disease were often difficult. The other five patients had a false-negative scan. Seven patients had a true-negative scan. No false-positive scans were found. Thus, the diagnostic accuracy for small-intestinal Crohn's disease was 85%. In contrast, of 32 patients with colonic disease (CD and UC), 26 had a true-positive scan corresponding in localization and extent with standard investigations, 3 patients had a false-negative scan (sensitivity, 90%), and 3 had a true-negative scan (diagnostic accuracy, 91%). The patients' acceptability of this procedure was definitely superior to that for radiology and endoscopy. In conclusion, this technique has a definite place in evaluating localization and extent of active colonic disease and in severely ill patients in whom invasive techniques are contraindicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Image quality and radiopharmaceutical parameters of indium-111 granulocytes in scintigraphy of inflammatory bowel disease.

This study was undertaken to investigate the influence of various parameters of injected autologous 111In labelled granulocytes on scintigraphic image quality. Forty-two scintigrams of 37 patients with inflammatory bowel disease were evaluated. The images were divided into three groups according to quality: good, intermediate and poor. The relationships between image quality and such radiopharmaceutical parameters as injected dose of 111In, number of injected cells and specific activity were investigated. It appeared that in order to obtain interpretable images, a specific activity of at least 85 kBq 111In/million cells was necessary. The activity of the injected dose must exceed 7 MBq if poor quality images and very long acquisition times are to be avoided.

Is radiolabelled sucralphate scintigraphy of any use in the diagnosis of inflammatory bowel disease?

Previous optimistic reports led us to undertake a study to determine the value of 99Tcm-sucralphate scintigraphy in the assessment of localization and extent of active inflammatory bowel disease. Eight patients were studied; four had Crohn's disease (three small bowel and one colon localization) and four patients had ulcerative colitis. The results obtained by scintigraphy were compared with those obtained by diagnostic radiology and/or endoscopy. In five patients indium-111 granulocyte scintigraphy was also performed. 99Tcm-sucralphate scans showed total discrepancy with standard investigations in four patients and partial discrepancy in the other four. Furthermore, it was difficult from the images to decide whether the radiolabelled sucralphate indicated true inflammation or normal distribution of the radiopharmaceutical. Patient acceptability was very low due to frequent scanning times and the recommended purgation which was not well tolerated and is contraindicated in severely ill patients. We conclude that this technique is not a good screening test for diagnosing inflammatory bowel disease and we have, therefore, discontinued the study.

Value of indium-111 granulocyte scintigraphy in the assessment of Crohn's disease of the small intestine: prospective investigation.

The present study was undertaken to determine the value of indium-111 granulocyte scintigraphy in Crohn's disease of the small bowel by comparing the results with those of radiology, endoscopy and surgery. Twenty-one patients with Crohn's disease of the small bowel, 9 patients with Crohn's disease of the colon, 1 patient with both localizations and 8 with ulcerative colitis were studied by indium-111 granulocyte scanning. Eighteen patients had evidence of active small intestinal disease based on clinical, radiologic, and/or endoscopic, and/or histopathological features. Thirteen of them had a true positive scan (sensitivity 72%), but accurate assessment of localization and extent of disease was often difficult. Five patients had a false negative scan and 4 a true negative. No false positive scans were found. The diagnostic accuracy was 77%. In contrast, from 18 patients with colonic disease, 16 had a true positive scan corresponding in localization and extent with standard investigations, 1 patient had a false negative scan (sensitivity 94%), and 1 a true negative (diagnostic accuracy 95%). This study also showed that 3-5 h scanning after injection of indium-111-labeled granulocytes is the optimal timing for this test. The patient's acceptability of this procedure was definitely superior to radiology and endoscopy. In conclusion, this technique has a definite place in evaluating localization and extent of active colonic disease, but it does not replace good small bowel radiology and should not be recommended in the routine diagnostic workup of Crohn's disease of the small intestine.