L Flood1, E Innala, R Löfberg, A-C Wikström. 1. Department of Gastroenterology and Hepatology, Novum, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden; IBD-Unit, HMQ Sophia Hospital, Solna, Stockholm, Sweden.
Abstract
BACKGROUND AND AIMS: Glucocorticosteroid treatment (GCS) is effective for attacks of ulcerative colitis (UC). However, 25-30% of patients fails to respond and may be considered steroid resistant. Glucocorticoid receptors (GR) mediate the effects of GCS. Colorectal mucosa levels of GR and NF-κB were analysed before, during and after treatment with GCS-compounds. METHODS: Patients with moderate-severe attacks of ulcerative colitis were included. Patients undergoing colonoscopy with normal finding served as controls. GR and NF-κB levels in colorectal mucosa were analysed by Western Blotting and the DNA-binding activity of NF-κB by EMSA. RESULTS: Twenty-eight patients and seven controls were included. Ten patients were judged clinically steroid resistant. Responders had significantly higher levels of GR in colorectal mucosa after one week of treatment than non-responders (P=0.039) and significantly higher levels of GR were found in responders in remission as compared to before treatment (P=0.013). NF-κB levels did not differ between the groups at first visit. Increasing levels were found only in responders as remission was obtained (P=0.031). EMSA detected 20% lower DNA-binding of NF-κB in responders in remission as compared to first visit (P=0.021). CONCLUSION: GR levels increase in UC-patients responding to GCS-therapy but not in steroid resistant patients and may be the reason for the lack of steroid-efficacy. Increasing NF-κB levels were found in responders attaining remission, possibly reflecting a lower turnover. A decrease in DNA-binding of NF-κB was found in these patients, perhaps because of the increased GR levels counteracting NF-κB activity.
BACKGROUND AND AIMS: Glucocorticosteroid treatment (GCS) is effective for attacks of ulcerative colitis (UC). However, 25-30% of patients fails to respond and may be considered steroid resistant. Glucocorticoid receptors (GR) mediate the effects of GCS. Colorectal mucosa levels of GR and NF-κB were analysed before, during and after treatment with GCS-compounds. METHODS:Patients with moderate-severe attacks of ulcerative colitis were included. Patients undergoing colonoscopy with normal finding served as controls. GR and NF-κB levels in colorectal mucosa were analysed by Western Blotting and the DNA-binding activity of NF-κB by EMSA. RESULTS: Twenty-eight patients and seven controls were included. Ten patients were judged clinically steroid resistant. Responders had significantly higher levels of GR in colorectal mucosa after one week of treatment than non-responders (P=0.039) and significantly higher levels of GR were found in responders in remission as compared to before treatment (P=0.013). NF-κB levels did not differ between the groups at first visit. Increasing levels were found only in responders as remission was obtained (P=0.031). EMSA detected 20% lower DNA-binding of NF-κB in responders in remission as compared to first visit (P=0.021). CONCLUSION: GR levels increase in UC-patients responding to GCS-therapy but not in steroid resistant patients and may be the reason for the lack of steroid-efficacy. Increasing NF-κB levels were found in responders attaining remission, possibly reflecting a lower turnover. A decrease in DNA-binding of NF-κB was found in these patients, perhaps because of the increased GR levels counteracting NF-κB activity.