Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans

Psychol Med. 2004 Oct;34(7):1289-97. doi: 10.1017/s0033291704001953.


Background: Elaboration of the concept of cytokine-induced sickness behaviour in recent years has opened new avenues for understanding brain involvement in sickness and recovery processes. Additionally, this has led to much speculation about the role of the immune system in neuropsychiatric syndromes, including depression and chronic fatigue. However, few studies have examined this phenomenon as it naturally occurs in sick humans, and none has attempted to document the quantitative relationships between cytokine levels and non-specific symptoms. The aim of this research was to examine human sickness behaviour and its immunological correlates in documented Epstein-Barr virus (EBV), Q fever or Ross River virus (RRV) infections.

Method: We studied two separate samples. The first consisted of 21 patients with acute Q fever. The second included 48 patients with acute RRV or EBV infection. Psychological and somatic symptom profiles were derived from self-report measures completed at enrolment. Quantification of proinflammatory cytokines [interleukin (IL)-1beta and IL-6] in sera and supernatants of peripheral blood mononuclear cell (PBMC) cultures was undertaken by specific ELISAs.

Results: Levels of IL-1beta and IL-6 spontaneously released from PBMC cultures were consistently correlated with reported manifestations of acute sickness behaviour including fever, malaise, pain, fatigue, mood and poor concentration.

Conclusions: IL-1beta and IL-6 produced as part of the host response represent sensitive markers of sickness behaviour in humans with acute infection. Further work is needed to systematically characterize the spectrum and natural history of sickness behaviour in humans and to elucidate its biological basis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Alphavirus Infections / immunology*
  • Alphavirus Infections / psychology
  • Cohort Studies
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / psychology
  • Female
  • Humans
  • Interleukin-1 / blood*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Q Fever / immunology*
  • Q Fever / psychology
  • Ross River virus / immunology*
  • Sick Role*
  • Statistics as Topic
  • Victoria


  • Interleukin-1
  • Interleukin-6