41. Immunogenetic and phenotypic explorations of the acute sickness response to common infections

Abstract

The host response to infection triggers a distinct set of physiological and behavioural changes termed the acute sickness response. Although this response is universal, individuals differ considerably in terms of the overall severity and the specific manifestations of acute sickness symptoms – suggesting host determinants. We examined the impact of functional polymorphisms in cytokine genes [tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ] on the overall illness severity and the specific symptom domains of fatigue, mood disturbance and cognitive impairment following acute infection with Epstein-Barr virus, Coxiella burnetii (Q fever), or Ross River virus in 300 participants in a prospective cohort study. We found that the IFN-γ +874 T/A, and the IL-10 −592C/A polymorphisms significantly affected illness severity ( p = 0.001), the production of pro-inflammatory cytokines ( p > 0.03), and the duration of illness. The high-producing IFN-γ +874 T allele was additionally associated with increased fatigue ( p = 0.0003), and the low-producing IL-10 −592 A allele with more severe neurocognitive impairment ( p = 0.017) and mood disturbance ( p = 0.044). The high producing G allele of IL-6-174 G/C polymorphisms also impacted on mood disturbance ( p = 0.05) after infection. The acute sickness response has discrete symptom domains including fatigue, mood and neurocognitive disturbance which have unique genetic associations. These findings provide the first phenotypic and immunogenetic analysis of different components of the acute sickness response in the setting of natural infection in humans.