TABLE 6

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.

DonorEC50EmaxEminHill SlopeR2
pg/ml% treated cells
Acetaminophen formation
    Hu1242135011823.8N.A.0.80
    Hu1242 + mAbN.D.N.D.N.D.N.D.N.D.
    Hu811087910529.0−2.790.84
    Hu8110 + mAbN.D.N.D.N.D.N.D.N.D.
6β-Hydroxytestosterone formation
    Hu124292.592.130.3−2.070.96
    Hu1242 + mAb173898.110.8−1.040.96
    Hu811063.683.921.6−1.100.88
    Hu8110 + mAb84993.523.0−1.080.92
  • 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.