Systemic inflammation is commonly accompanied by unspecific bodily and psychological symptoms of sickness that are relevant to highly prevalent health conditions. These sickness symptoms significantly contribute to overall disease burden and may also arise as unwanted side effects during immunotherapies or vaccinations, negatively affecting health-related quality of life and treatment adherence. While placebo research robustly demonstrates the impact of positive expectations on disease-specific symptoms and therapeutic outcomes, it remains unclear, whether positive expectations can alleviate inflammation-induced sickness symptoms in the context of immunomodulatory treatments. To address this gap, this thesis employed the established experimental endotoxemia model within a fully balanced 2 x 2 factorial placebo design. In total, N=124 healthy volunteers randomly received active anti-inflammatory (i.e., ibuprofen, 600 mg per os) or inert placebo treatment, combined with verbal information to induce positive or neutral treatment-related expectations. Subsequently, all volunteers were injected with Lipopolysaccharide (LPS, 0.8 ng/kg of bodyweight) to induce acute systemic inflammation and related symptoms. Ibuprofen effectively reduced both self-reported bodily and affective sickness symptoms during experimental endotoxemia, as well as LPS-induced hyperalgesia (assessed via pressure pain thresholds). Positive expectations alleviated bodily and affective symptoms (even among volunteers receiving placebo) and enhanced actual ibuprofen efficacy for affective symptoms. Exploratory analyses based on these findings suggested that expectation and medication interact differently across symptom domains, with additive effects observed for affective symptoms and subadditive effects for bodily sickness symptoms. Contrary to self-reported symptoms, LPS-induced hyperalgesia was unaffected by positive expectations. Moreover, we found no expectation effects on peripheral-physiological parameters, indicating that expectation-induced subjective symptom improvement may be mediated via mechanisms distinct from direct peripheral immune modulations. Together, these findings underscore the complex interplay between pharmacological and psychological treatment components in shaping the experience of inflammation-induced sickness symptoms, and highlight the potential of utilizing treatment expectations, e.g., via targeted healthcare communication, to optimize therapeutic regimes involving inflammation-induced sickness symptoms.
Justine Schmidt (Wed,) studied this question.