Regulatory T cells (Treg) are critical in maintaining immune tolerance and suppressing autoimmunity. The transcription factor Foxp3 serves as a master switch that controls the development and function of Treg. Foxp3 expression is epigenetically regulated by DNA methylation, and DNA methyltransferase (DNMT) inhibitors can induce Foxp3 expression in naive CD4+ T cells. We showed that EGCG, a major green tea polyphenol, could act as a dietary DNMT inhibitor, and induced Foxp3 and IL-10 expression in CD4+ Jurkat T cells at physiologically relevant concentrations in vitro. We further showed that mice treated with EGCG in vivo had significantly increased Treg frequencies and numbers in spleen and lymph nodes and had inhibited T cell response. Induction of Foxp3 expression correlated with a concomitant reduction in DNMT expression and a decrease in global DNA methylation. Our data suggested that EGCG can induce Foxp3 expression and increase Treg frequency via a novel epigenetic mechanism. While the DNMT inhibitory effects of EGCG was not as potent as pharmacologic agents such as 5-aza-2′-deoxycytidine, the ability of dietary agents to target similar mechanisms offers opportunities for potentially sustained and longer-term exposures with lower toxicity. Our work provides the foundation for future studies to further examine and evaluate dietary strategies to modulate immune function.

Background: Following availability in the United States in 2011, intravenous acetaminophen (IV APAP) was added to many hospital formularies for multimodal pain control. In 2014, the price of IV APAP increased from $12/g to $33/g and became a top 10 medication expenditure at our institution. Objective: To promote appropriate IV APAP prescribing and reduce costs. Design, Setting, Participants: Quality improvement project at a 562-bed academic medical center involving all inpatient admissions from 2010 to 2017. Interventions: Using Plan-Do-Study-Act (PDSA) methodology, our Pharmacy & Therapeutics (P&T) committee aimed to reduce inappropriate use of IV APAP by refinement of restriction criteria, development of clinical decision support in the electronic medical record, education of clinical staff on appropriate use, and empowerment of hospital pharmacists to enforce restrictions. Measurements: Monthly IV APAP utilization and spending were assessed using statistical process control charts. Balancing measures included monthly usage of IV opioid, IV ketorolac, and oral ibuprofen. Results: Five PDSA cycles were conducted during the study period. Monthly spending on IV APAP decreased from the highest average of $56 038 per month to $5822 per month at study conclusion. Interventions resulted in an 80% annual cost savings, or an approximate savings of $600 000 per year. Usage of IV opioids, IV ketorolac, and oral ibuprofen showed no major changes during the study period. Conclusions: IV APAP can be restricted in a safe and cost effective manner without concomitant increase in IV opioid use.