Procedures

The study was conducted between March 2011 and August 2013 at the UCLA Clinical and Translational Research Center (CTRC) using a randomized, double-blind, placebo-controlled design. Briefly, each participant randomly received either low-dose endotoxin (0.8 ng kg⁻¹ of body weight, Escherichia coli group O:113) or placebo (same volume of 0.9% saline) as an intravenous bolus. Endotoxin administration mimics the increases in inflammation that are found in inflammatory disorders, infections and also psychological stress.^{27, 28, 29} In the current study, endotoxin administration led to about 10-fold increase in interleukin-6 (IL-6) levels and fivefold increase in tumor necrosis factor-α (TNF-α) levels (by comparing geometric means), which may correspond to real-world clinical settings such as human immunodeficiency virus infection²⁷ and rheumatoid arthritis.³⁰ Blood samples (to assess circulating cytokine levels) were collected at baseline (T0) and then approximately every hour post injection for the next 6 h (T1–T6). The participants also completed hourly measures of mood and sickness symptoms.