Resistance to steroids only becomes apparent when

the ind

Resistance to steroids only becomes apparent when

the individual develops a disease that requires steroid pharmacotherapy.28 Our data therefore STA-9090 clinical trial suggests that such intrinsic steroid resistance plays a significant role in the failure to respond to steroid therapy in SAH. This finding is consistent with previous reports in other conditions, such as ulcerative colitis,13, 16, 29 asthma,12 rheumatoid arthritis,15 and a very recent report in AH.11 In this study, early bilirubin change correlated with in vitro steroid sensitivity (Imax). Our study adds to this report by demonstrating that in vitro steroid resistance also correlates with a hard clinical endpoint, namely, death. This was possible in our study as we had more patients (n = 20 versus n = 12) and more deaths (11 versus 4), and we would anticipate that extension of the study of Kendrick et al.11 to a further follow-up and/or a larger cohort would lead to C646 similar conclusions. No correlation was seen between measures of baseline disease severity (MdF score, Glasgow score, Lille score) and outcome in response to steroids in this cohort (Fig. 1). Although some previous studies relating baseline disease severity in AH to clinical response have shown a correlation with outcome, these studies have included all grades of disease severity and not specifically correlated outcome in the most severe group treated with steroids.

The lack of correlation with disease severity in our cohort emphasizes that the failure to respond adequately to steroids in some individuals is not simply explained by differences in baseline disease severity and that the role played by intrinsic steroid resistance in determining outcome is independent of disease severity. Consistent with previous reports,1, 25, 30-37 we did observe in our cohort a correlation between fall in bilirubin by day 7 (a measure of early response rather than disease severity) and long-term outcome (Fig. 1). The separation in outcome between individuals determined to be steroid-resistant or steroid-sensitive at baseline was not complete (Fig. 3). Hence, measurement of in vitro steroid sensitivity should not be considered a robust predictive marker for

use in clinical 上海皓元医药股份有限公司 management. Rather, the present finding provides evidence for an important factor that contributes to outcome, and which might represent a target for pharmacotherapy to improve overall outcomes. In this context, we noted that that addition of basiliximab to in vitro cell cultures, competitively targeting CD25, a key component of the high-affinity IL-2 receptor,38 improved steroid sensitivity in all individuals with low Imax on the DILPA test, consistent with previous reports in ulcerative colitis.16, 29, 39 The mechanisms involved in steroid resistance are unknown but IL-2 may play an important immunological role. Combination of IL-2 and IL-4 has been shown to reduce glucocorticoid receptor-binding affinity and consequent T-cell response to steroids.

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