Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.

The relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].

Please format your output as a JSON array. Each entry in the array should express a single relation, formatted as ["<Entity_A>", "<RELATION_A_B>", "<Entity_B>"]. If no relations can be found, please output an empty JSON array [].

Abstract:

A Physiologically-Based Pharmacokinetic Modelling Approach to Predict Disease-Drug Interactions: Suppression of CYP3A by IL-6. Elevated cytokine levels can down-regulate expression of cytochrome P450 enzymes (CYPs) and suppress their activity. Treatment of inflammation or infection with cytokine-modulating therapeutic proteins (TP) could reverse suppression manifesting as therapeutic protein-drug drug interactions (TP-DDI). A physiologically-based pharmacokinetic model was used to quantitatively predict the impact of IL-6 on sensitive CYP3A4 substrates. Elevated simvastatin AUC in virtual rheumatoid arthritis patients, following 100 pg/mL of IL-6 was comparable to observed clinical data (59% versus 58%). In virtual bone marrow transplant (BMT) patients, 500 pg/ml of IL-6 resulted in increase in cyclosporine AUC that was in good agreement with the observed data (45% versus 39%). In a different group of BMT patients treated with cyclosporine, the magnitude of interaction with IL-6 was under predicted ~3-fold. The complexity of TP-DDI highlights underlying pathophysiological factors to be considered but these simulations provide valuable first steps towards predictions of TP-DDI risk. Clinical Pharmacology & Therapeutics (2013); accepted article preview online 10 April 2013 doi:10.1038/clpt.2013.79.
[["cyclosporine", "REGULATOR", "IL-6"]]