P082 Anti-TNF-alpha therapy and apoptosis
R. Zaharie1, F. Zaharie2, A. Tantau*3, B. Petrushev4, M. Tantau4
1University of Medicine and Pharmacy, Third Medical Clinic, Cluj-Napoca, Romania, 2University of Medicine and Pharmacy, Third Surgery Clinic, Cluj-Napoca, Romania, 3University of Medicine and Pharmacy, Fourth Medical Clinic, Cluj-Napoca, Romania, 4University of Medicine and Pharmacy, Third Medical Clinic, Cluj-Napoca, Romania
Research of intimate mechanism of anti-TNF-alpha led to emphasis on the involvement of this therapy in intestinal epitelial cells apoptosis. Mechanism of action of anti-TNF-alpha therapy consist of induction of apoptosis of T lymfocites and reduction of intestinal cell apoptosis. We aim to investigate the modifiation of apoptotic ratio after the anti-TNF-alpha induction therapy and to correlate the magnitude of that modifiation with the endoscopic response.
Included in the study were 27 patients with ulcerative colitis with the indication of anti-TNF-alpha therapy admitted consecutively in the Institute of Gastroenterology and Hepatology Cluj-Napoca. We evaluated the apoptotic ratio of intestinal epitelial cells by using immunostaining method TUNEL on the biopsy specimens taken before and after the adminstration of anti-TNF-alpha therapy. We evaluated at the same time the presence of mucosal healing after the induction therapy.
Determination of epitelial apoptotic ratio was performed before and after induction therapy. There is a clear decrease in the rate of intestinal cell apoptosis after the induction therapy compared with biopsies taken before. Thus, the mean apoptotic ratio before initiating anti-TNF-alpha therapy was 74.67% (44%–94%), and after initiation of anti-TNF-alpha therapy was 24.33% (5%–45%). The difference between these 2 values was significant: OR: 50.33 (CI95%: 43.29–57.38), p < 0.001. The decrease in apoptotic ratio was significantly higher in patients who achieved mucosal healing (median, 62%) compared with those without mucosal healing (median 39.5%), p < 0.001.
Anti -TNF-alpha therapy induces apoptosis of intestinal epithelial cells with a significant decrease in the apoptotic ratio at the end of induction therapy, which correlates very well with the presence of mucosal healing.