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

Abstract

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.

Does Human Experimental Endotoxemia Impact Negative Cognitions Related to the Self?

“…We observed the expected transient increases in circulating pro-inflammatory cytokines and body temperature, indicating systemic inflammation in response to low-dose LPS. Self-reported positive mood showed a transient decline after LPS application, which is in line with the well-established effects of LPS-induced systemic inflammation on mood (Reichenberg et al, 2001 ; Wright et al, 2005 ; Eisenberger et al, 2009 ; Hannestad et al, 2011 ; Benson et al, 2017a , b ; Engler et al, 2017 ), and with previous reports documenting an association between dysthymia and LPS-induced increases in cytokine concentrations in plasma (Reichenberg et al, 2001 ; Eisenberger et al, 2010b ) and cerebrospinal fluid (Engler et al, 2017 ).…”

“…,” or “ how confident are you that other people think you are attractive? ” One likely explanation for the reported reduction in body-related self-esteem is that pro-inflammatory mediators released in response to LPS reportedly induce physical sickness symptoms such as fatigue and pain (Lekander et al, 2016 ; Benson et al, 2017b ). Such symptoms conceivably impact self-perceived physical abilities, and hence the subscale of the questionnaire employed herein.…”

“…Cognitive symptoms of depression were assessed with three validated questionnaires (see below) 3 h post injection. This time point was chosen for two reasons: First, increased plasma concentrations of tumor necrosis factor (TNF)-α and IL-6 were consistently observed 2–4 h post injection in previous studies, indicating systemic immune activation (Wegner et al, 2014 ; Benson et al, 2017b ). More importantly, we found a significant rise in IL-6 in the cerebrospinal fluid 3 h post-injection (Engler et al, 2017 ), reflecting a CNS response to peripheral inflammation.…”

“…Sickness behavior shows striking similarities to several key symptoms of depression, although sickness behavior symptoms are transient and typically disappear when inflammation has resolved (Dantzer et al, 2008 ; Raison and Miller, 2011 ). Low doses of endotoxin reliably induce transient symptoms including negative mood (Reichenberg et al, 2001 ; Wright et al, 2005 ; Eisenberger et al, 2009 , 2010b ; Hannestad et al, 2011 ; Benson et al, 2017a ; Engler et al, 2017 ), feelings of social isolation and disturbed psychosocial functioning (Eisenberger et al, 2009 , 2010b ; Inagaki et al, 2015 ; Moieni et al, 2015a , b ), changes in motivation (Eisenberger et al, 2010a ; Lasselin et al, 2017 ) and fatigue (Benson et al, 2017b ).…”

Pilot investigation into the sickness response to influenza vaccination in adults: Effect of depression and anxiety

“…Despite evidence of altered immune response to vaccination in individuals with depression and stress, there is no literature that demonstrates a greater behavioral sickness response to influenza vaccine in those with mental illness. However, subclinical depression scores in healthy participants have been shown to predict physical sickness symptoms following LPS administration (19), warranting further examination of behavioral immune response in the context of mental illness. The primary purpose of this project was to interrogate behavioral immune response in participants with depression or anxiety compared to healthy participants.…”