Ultrastructural evidence of mucosal healing after infliximab in patients with ulcerative colitis.
BACKGROUND
Infliximab is a monoclonal anti-TNF-alpha antibody that has been shown to be effective in Crohn's disease therapy. However, data are scarce about the mechanism of action and its efficacy in ulcerative colitis (UC).


OBJECTIVE
To assess intracellular changes of the colonic mucosa in patients with UC before and after infliximab treatment.


METHODS
7 patients (18-65 years, 4 men) with active, refractory, moderate to severe UC (Lichtiger's Clinical Activity Index > 6, Endoscopic Index > 4) underwent colonoscopy before and 4 weeks after the initial infusion of infliximab 5mg/kg of body weight. Endoscopically obtained biopsy specimens were processed specifically, stained with uranyl-acetate and lead citrate and examined with a JEOL-1010 transmission electron microscope.


RESULTS
Before treatment we noticed severe alterations of the epithelium: microvilli depletion, shattering of the epithelial junctions, cytoplasmic vacuolization, dilatation of the endoplasmic reticulum, pycnotic nuclei, altered structure of mitochondria and Golgi complexes. Rarefaction of the goblet cells, and abnormal mucus formation and secretion were also observed. The corresponding chorion showed structural alteration of component cells, obstructed capillaries, erythrocyte extravasation, and many plasmocytes and neutrophils. After infliximab, improvement in morphology and function of the epithelial organelles, rich mucus secretion and recovery of the chorionic components were noticed.


CONCLUSIONS
Our study revealed important intracellular alterations of the UC mucosa that were restored after infliximab therapy. These features may contribute to a better understanding of UC pathogenesis and mechanism of action of the anti-TNF-alpha therapies.
Fratila
Ovidiu C
OC
3rd Medical Clinic, Faculty of Medicine and Pharmacy, Oradea, Romania. ovidiuf@rdslink.ro
Craciun
Constantin
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D003113:Colonoscopy; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D012383:Romania; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014945:Wound Healing / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab