What Makes You Feel Sick After Inflammation? Predictors of Acute and Persisting Physical Sickness Symptoms Induced by Experimental Endotoxemia

Clin Pharmacol Ther. 2017 Jul;102(1):141-151. doi: 10.1002/cpt.618. Epub 2017 Mar 25.


We aimed to identify statistical predictor variables of lipopolysaccharide (LPS)-induced physical sickness symptoms during the acute and late inflammatory phases using multivariate regression analyses. Data from N = 128 healthy volunteers who received i.v. LPS injection (0.4 or 0.8 ng/kg) or placebo were pooled for analyses. Physical sickness symptoms experienced during the acute (0-6h postinjection) and late (6-24h postinjection) phases were assessed with the validated General-Assessment-of-Side-Effects (GASE) questionnaire. LPS-treated subjects reported significantly more physical sickness symptoms. Physical symptoms during the acute phase were associated with LPS-induced mood impairments and interleukin (IL)-6 increases, explaining 28.5% of variance in GASE scores. During late phase, LPS-induced increases in cortisol and IL-6 plasma concentrations and baseline depression were significant predictor variables, explaining 38.5% of variance. In patients with recurrent or chronic inflammatory states, these factors may act as risk factors ultimately contributing to an exacerbation of sickness symptoms, and should be considered as potential targets for therapeutic strategies.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affective Symptoms* / diagnosis
  • Affective Symptoms* / etiology
  • Endotoxemia* / etiology
  • Endotoxemia* / immunology
  • Endotoxemia* / physiopathology
  • Endotoxemia* / psychology
  • Healthy Volunteers
  • Humans
  • Hydrocortisone / analysis*
  • Inflammation* / etiology
  • Inflammation* / immunology
  • Interleukin-6 / analysis*
  • Lipopolysaccharides* / administration & dosage
  • Lipopolysaccharides* / immunology
  • Male
  • Pain* / diagnosis
  • Pain* / etiology
  • Research Design
  • Surveys and Questionnaires
  • Symptom Assessment / methods
  • Time Factors


  • Interleukin-6
  • Lipopolysaccharides
  • Hydrocortisone