Effect of short-term topical corticosteroid treatment on mucosal enzyme systems in patients with distal inflammatory bowel disease.
OBJECTIVE
Glucocorticoids, even when administered topically, have a known early benefit on diarrheal symptoms in inflammatory bowel diseases which may not be explained exclusively by their anti-inflammatory effect. Therefore, we evaluated a possible early effect of topically administered glucocorticosteroids on the mucosal function of patients with distal inflammatory bowel disease in a prospective, controlled study, which was blinded for histological evaluation.


METHODS
Eleven patients with distal ulcerative colitis or Crohn's disease, and 8 patients without intestinal inflammation were studied. A sigmoidoscopy with biopsy sampling (8-10) was performed before and 3 days after rectal administration of a hydrocortisone acetate foam preparation (100 mg b.i.d.). Prior to and after topical steroid treatment, basolateral (Na++K+)-ATPase activity (coupled optical assay), specific 3H ouabain binding (rapid filtration method), 5'-nucleotidase (microdetection method of phosphorus), and mucosal DNA levels (diphenylamine reaction) were determined from biopsy homogenates. Morphological and clinical characteristics were assessed according to established scores.


RESULTS
Short-term topical GCS treatment significantly (p<0.05) stimulated (Na++K+)-ATPase activity (103%) as well as the number of active (Na++K+)-ATPase molecules (190%). In the healthy mucosa, only (Na++K+)-ATPase activity was stimulated (124%, p<0.05; specific 3H ouabain binding: 33%; p=0.09). As an unspecific GCS effect, apical 5'-nucleotidase was also stimulated (p<0.05; IBD: 50%; controls: 200%). As assessed by endoscopic and histological scores, as well as by mucosal DNA levels, morphological signs of intestinal inflammation remained unchanged during the study, whereas the daily stool frequency decreased significantly (p<0.05).


CONCLUSIONS
In patients with distal inflammatory bowel disease, short-term treatment with topical GCS leads to a quick recovery from diarrheal symptoms, due to the early improvement of mucosal function prior to the occurrence of the well-known anti-inflammatory GCS effect.
Scheurlen
C
C
Department of General Internal Medicine, University of Bonn, Germany.
Allgayer
H
H
Hardt
M
M
Kruis
W
W
D015720:5'-Nucleotidase / Q000378:metabolism; D000285:Administration, Rectal; D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D004247:DNA / Q000032:analysis; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; C021650:hydrocortisone acetate; D004247:DNA; D015720:5'-Nucleotidase; D000254:Sodium-Potassium-Exchanging ATPase; D006854:Hydrocortisone