Effects of IL-6 on CYP3A4 in hepatocytes
| Basal Activity | Maximum CYP3A4 Suppression | IC50 for CYP3A4 Suppression | CRP mRNA Expression | Max CYP3A4 Induction | |||
|---|---|---|---|---|---|---|---|
| CYP3A4 Activity | CYP3A4 Activity | CYP3A4 mRNA | CYP3A4 Activitya | CYP3A4 mRNAb | Maximum fold increase | EC50a | CYP3A4 mRNA |
| pmol/min/106 cells | % suppression | % suppression | pg/ml | pg/ml | ng/ml | fold induction | |
| Company A | |||||||
| 5.0 (−dex) | 20c (−dex) | ND | NMd (−dex) | ND | ND | ND | ND |
| Company B | |||||||
| 7.0 (−dex) | 38e (−dex) | 78e (−dex) | 217 (−dex) | 18.5 (+dex) | 208 (−dex) | 0.114 (−dex) | 2130 |
| 27 (+dex) | 74e (+dex) | 99.6e (+dex) | 24 (+dex) | 572 (+dex) | 0.950 (+dex) | ||
| Company C | |||||||
| NMf | ND | 93e (+dex) | ND | 11.6 (+dex) | ND | ND | 7 |
| Company D | |||||||
| 5.9 (−dex) | ND (−dex) | 95e (−dex) | ND (−dex) | ND (−dex) | 1000 (−dex) | 346 (−dex) | 4 |
| 13 (−dex) | 91e (+dex) | 55e (-dex) | 1750 (+dex) | 1600 (+dex) | 1342 (+dex) | 48 (+dex) | |
| 220 (+dex) | 68e (+dex) | 99e (+dex) | 600 (+dex) | ||||
| 93 (+dex) | 99e (+dex) | ||||||
| Company E | |||||||
| ND | NM (−dex) | 56c (−dex) | NMd (−dex) | 8.3 (+dex) | >21g (−dex) | >500h (−dex) | 369 |
| NM (+dex) | 94c (+dex) | NMd (+dex) | >35g (+dex) | >500h (+dex) | |||
| Company F | |||||||
| 2.7 (−dex) | 39e (−dex) | 94e (−dex) | NMd (−dex) | 94.7(−dex) | ND | ND | 7 |
| Summary | |||||||
| 2.7-13 (−dex) | 20-38 (−dex) | 55-95 (−dex) | 217 (−dex) | 94.7 (−dex) | 208-1000 (−dex) | 0.114-346 (−dex) | ND |
| 27-220 (+dex) | 68-91 (+dex) | 93-99.6 (+dex) | 24-1750 (+dex) | 8.3-1600 (+dex) | 572-1342 (+dex) | 0.950-47.5 (+dex) | |
dex, dexamethasone; ND, not determined; NM, not measurable.
↵a Reported IC50 and EC50 values were calculated uniquely by each laboratory that generated the respective data set.
↵b Reported absolute IC50 values were calculated with data collated across companies and uniformly analyzed using GraFit v.5.0.8 (Erithacus Software Ltd., Surrey, UK) and 4-parameter equation fitting.
↵c Maximum suppression achieved at concentrations ≥10 ng/ml.
↵d Not measurable due to less than 50% CYP3A4 suppression.
↵e Maximum suppression achieved at concentrations ≥100 ng/ml.
↵f Not measurable due to low turnover rates in control.
↵g Observed highest fold increase in CRP; maximum fold increase in CRP was not achieved within the concentration range studied.
↵h EC50 assumed to be greater than the highest concentration studied.