Psoriasis is a T-cell-mediated autoimmune disease involving the skin. Two 
cytokines, interleukin-12 (IL-12) and IL-23 have been shown to play a pivotal 
role in the pathogenesis of the disease. Ustekinumab (Stelara) is a therapeutic 
monoclonal antibody (mAb) targeted against the p40 shared subunit of IL-12 and 
IL-23. Recently the ability of therapeutic proteins (TP) including mAbs that 
target either cytokines directly (e.g., Pegasys; peginterferon α-2a) or their 
respective cell surface receptors [e.g., tocilizumab (Actemra); anti IL-6R] to 
desuppress cytochrome P450 (P450) enzymes in vitro and in the clinic, has been 
demonstrated. In the present study the ability of IL-12 and IL-23 to suppress 
multiple P450 enzymes was investigated in vitro using six separate lots of 
cultured human hepatocytes. Following exposure of 10 ng/ml IL-12 and IL-23 for 
48 hours, either alone or in combination, no change in CYP2B6, 2C9, 2C19, or 3A4 
gene expression or functional activity was observed. None of the untreated 
hepatocyte donors showed appreciable expression of the IL-12 or IL-23 receptors. 
Similar results were seen with whole human liver samples. Exposure of 
hepatocytes to IL-12 and/or IL-23, known P450 suppressors (IL-6 and tumor 
necrosis factor-α) or known P450 inducers (β-naphthoflavone, phenobarbital, and 
rifampicin) did not appreciably alter the expression of the IL-12 and IL-23 
receptors either. Finally, in contrast to the positive control IL-6, expression 
of the acute phase C-reactive protein was unaltered following IL-12 and/or IL-23 
treatment. Together, these data suggest a negligible propensity for IL-12 or 
IL-23 to directly alter P450 enzymes in human hepatocytes.