Increased nuclear factor-kappaB activation in colitis of interleukin-2-deficient mice

Recent studies support nuclear factor-kappaB (NF-kappa B) as a critical transcription factor in inflammatory bowel disease, We examined NF-kappa B and its inhibitors, I kappa B-alpha and I kappa B-beta, In the colitis of interleukin-2 deficient (IL-2(-/-)) mice at the ages of 5, 10, and 15 weeks and compared them with those of age-matched wild-type mice. Colon levels of nuclear NF-kappa B and mRNA for NF-kappa B responsive cytokines interleukin-1 beta and tumor necrosis factor-alpha were markedly increased in interleukin-2(-/-) mice. Colon interleukin-1 beta protein levels were significantly elevated, consistent with increased interleukin-1 beta mRNA, whereas tumor necrosis factor-alpha protein levers were either Tower than those of the control group or did not differ. Protein levels of the immunomodulatory cytokine interleukin-10 were df minished. The NF-kappa B responsive I kappa B-alpha, was also increased, mirroring NF-kappa B activation. In contrast, I kappa B-beta levels did not differ from those of wild-type mice in the 5- and 10-week groups and were only mildly increased in the 15-week group. Serum amyloid A, an acute phase protein that also is NF-kappa B-responsive, was dramatically elevated in the serum of interleukin-2(-/-) mice and correlated with the severity of the colitis. These data support a role for NF-kappa B in the pathogenesis of intestinal inflammation in interleukin-2(-/-) mice. The measurement of NF-kappa B in colon tissue samples may provide a sensitive means of assessing the state of activation of the mucosal immune response, and serum amyloid A appears to be a reliable biochemical marker of disease activity.