Editor,—In their recent paper (Gut1998;42:477–84) Schreiber and coworkers demonstrated that RelA (p65) is present in nuclear extracts of biopsy specimens or lamina propria mononuclear cells from patients with active inflammatory bowel disease (IBD). Furthermore, they show NFκB binding activity and a corresponding decrease in IκBα in lamina propria mononuclear cells treated with lipopolysaccharide (LPS). In contrast, treatment with dexamethasone prevented LPS induced nuclear translocation of NFκB due to persistence of IκBα. The authors conclude from these data that corticosteroids inhibit NFκB activation in vitro by stabilising the cytosolic inhibitor IκBα against activation induced degradation.

Firstly, this conclusion cannot be drawn from the data presented in the paper. Secondly, their conclusion contradicts a number of previously published observations.

Two models of corticosteroid mediated NFκB inhibition have been proposed. The first proposes that down modulation of κB driven genes results from a physical interaction between the glucocorticoid receptor and the RelA (p65) subunit. Negative cross-talk between the glucocorticoid receptor and RelA is due to direct interaction via the Rel homology …