Objective: It has been proposed that aberrant immunity of local bowel mucosa may cause ulcerative colitis (UC) and the tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappa B (NF-kappa B) may play a role in the development of this disease. To investigate the role of TNF-alpha and NF-kappa B in childhood UC, the expression of TNF-alpha and NF-kappa B in the bowel mucosa and their relationship were studied.
Methods: Using anti-CD68, anti-TNF-alpha and anti-NF-kappa Bp65 antibodies, the cytokine immunoreactivities in the bowel mucosa of 39 cases of childhood UC (active UC: n = 21, non-active UC: n = 18) were detected by immunohistochemistry. The control specimens of normal bowel mucosa were collected from 7 cases with colorectal polyp or abdominal pain by sigmoidoscopy.
Results: The numbers (median: interquartile range) of CD68(+) cells, TNF-alpha(+) cells and NF-kappa Bp65(+) cells were 44.0 (31.5 - 48.2), 42.7 (19.5 - 65.0) and 50.7 (30.0 - 58.0) in the active UC mucosa, and were 9.2 (7.9 - 16.6), 5.5 (2.5 - 9.1) and 4.2 (3.0 - 8.4) in non-active UC mucosa, and 5.3 (4.3 - 8.7), 3.0 (0.0 - 6.3) and 3.3 (0.0 - 4.0) in the control mucosa, respectively. The levels of CD68, TNF-alpha and NF-kappa Bp65 expressions in the active UC were significantly higher than those in the non-active UC (P < 0.001) and the controls (P < 0.001). The expression level of CD68 in non-active UC was much higher than that in the controls (P = 0.008). Using the correlation analysis, a positive correlation between TNF-alpha and NF-kappa B activation was found (r = 0.885, P < 0.001).
Conclusions: Macrophages TNF-alpha and NF-kappa B may play an important role in the pathophysiologic mechanism of childhood active UC. The activation of NF-kappa B may be associated with the release of TNF-alpha.