Effects of an IL-6-neutralizing monoclonal antibody on the suppression of CYP1A2 and CYP3A4 activity in human hepatocytes treated with IL-6
Hepatocytes were treated for 72 h with IL-6 in the presence or absence of 100 ng/ml of IL-6-neutralizing antibody. The measured Kd value of the monoclonal antibody was 1.7 nM.
| Donor | EC50 | Emax | Emin | Hill Slope | R2 |
|---|---|---|---|---|---|
| pg/ml | % treated cells | ||||
| Acetaminophen formation | |||||
| Hu1242 | 1350 | 118 | 23.8 | N.A. | 0.80 |
| Hu1242 + mAb | N.D. | N.D. | N.D. | N.D. | N.D. |
| Hu8110 | 879 | 105 | 29.0 | −2.79 | 0.84 |
| Hu8110 + mAb | N.D. | N.D. | N.D. | N.D. | N.D. |
| 6β-Hydroxytestosterone formation | |||||
| Hu1242 | 92.5 | 92.1 | 30.3 | −2.07 | 0.96 |
| Hu1242 + mAb | 1738 | 98.1 | 10.8 | −1.04 | 0.96 |
| Hu8110 | 63.6 | 83.9 | 21.6 | −1.10 | 0.88 |
| Hu8110 + mAb | 849 | 93.5 | 23.0 | −1.08 | 0.92 |
N.A., not applicable: Hu1242 was fit to a bell-shaped dose-response model as described under Materials and Methods. N.D., data could not be fit to any dose-response model.