Infliximab therapy decreases the levels of TNF-alpha and IFN-gamma mRNA in colonic mucosa of ulcerative colitis.
OBJECTIVE
The mechanisms of action of infliximab (IFX) in the treatment of ulcerative colitis (UC) are poorly understood. The aim of the study was to investigate the changes in tissue expression of tumor necrosis factor-alpha (TNF-alpha) and other cytokines in UC patients receiving IFX treatment.


METHODS
The levels of TNF-alpha, interleukin (IL)-10, IL-4, and interferon-gamma (IFN-gamma) mRNA in colonic biopsies from 32 UC patients during IFX treatment were measured by real-time polymerase chain reaction (PCR) and compared with those of 19 controls. Immunohistochemistry was performed to characterize the changes of inflammatory cells during treatment.


RESULTS
IFX reduced the expression of TNF-alpha and IFN-gamma mRNA, but not that of IL-10 and IL-4 mRNA. Reductions in TNF-alpha mRNA were correlated to clinical and endoscopic improvements, and normalization of TNF-alpha mRNA was obtained in patients with healed mucosa. The numbers of T lymphocytes and macrophages were significantly decreased in patients with healed mucosa after IFX treatment, although compared to normal controls, there were still increased levels of TNF-alpha-positive cells after treatment.


CONCLUSIONS
IFX induced down-regulation of the mucosal TNF-alpha and IFN-gamma mRNA expression in UC patients. The numbers of T lymphocytes and macrophages were significantly decreased in patients with endoscopically healed mucosa after IFX treatment.
Olsen
Trine
T
Laboratory of Gastroenterology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. Trine.Olsen@fagmed.uit.no
Cui
Guanglin
G
Goll
Rasmus
R
Husebekk
Anne
A
Florholmen
Jon
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D015870:Gene Expression; D006801:Humans; D000069285:Infliximab; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D000069285:Infliximab