Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes

Background-Up to 29% of patients with severe ulcerative colitis (UC) fail t o respond to steroid treatment and require surgery. Previous studies have f ailed to show a clear correlation between failure of steroid treatment in s evere UC and measures of disease severity. The reasons for treatment failur e therefore remain unknown. Aim-To investigate the hypothesis that patients with severe UC who fail to respond to steroid treatment have steroid resistant T lymphocytes, Methods-Eighteen patients with severe UC were studied. After seven days' tr eatment with high dose intravenous steroids they were classified as complet e responders (CR), incomplete responders (IR), or treatment failures (TF), Within 48 hours of admission blood was taken and the antiproliferative effe ct of dexamethasone on phytohaemagglutinin stimulated peripheral blood T ly mphocytes was measured. Maximum dexamethasone induced inhibition of prolife ration (I-max) was measured. Results-In vitro T lymphocyte steroid sensitivity of TF and IR patients was significantly less than that of CR patients. Both TF and 3/5 IR patients h ad an I-max of less than 60%; all CR patients had an I-max of greater than 60%. No significant correlation was seen between response to treatment and disease severity on admission. When in vitro T lymphocyte steroid sensitivi ty was remeasured three months later, there was no difference between the g roups. Conclusions-Results suggest that T lymphocyte steroid resistance is an impo rtant factor in determining response to steroid treatment in patients with severe UC and may be more predictive of outcome than disease severity.