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

Vollmer-Conna U, Fazou C, Cameron B, Li H, Brennan C, Luck L, Davenport T, Wakefield D, Hickie I, Lloyd A.
Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behavior in humans.
Psychological Medicine 34:1-9, 2004.

Summary

Cytokines are chemical substances that act upon other cells and are secreted by the immune system. When there is an infection, cytokines are stimulated, and patients start manifesting "acute sickness behavior" symptoms (i.e., fatigue, increased sleep, malaise, listlessness, inability to concentrate, subjective feelings of poor memory, fever, and decreased appetite). Cytokines have been hypothesized to play a part in CFS, but it is not clear whether cytokines are correlated with these symptoms in either acute infections or CFS. Australian investigators who collaborate in the CDC CFS research program collected information on patients with infectious mononucleosis (caused by Epstein-Barr virus), Q fever, and a mosquito-transmitted disease called Ross River virus (RRV). These diseases appear similar clinically, and at least 10% appear to progress to an illness similar to CFS. The study found that levels of two cytokines, IL-1b and IL-6, consistently correlated with reported manifestations of acute sickness behavior, including fatigue, mood, poor concentration, fever, malaise, and muscle/joint pain. Further work is needed to confirm these cytokines as biological markers for acute sickness behavior in humans.

Abstract

Background: Elaboration of the concept of cytokine-induced sickness behavior 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 behavior and its immunological correlates in documented Epstein-Barr virus (EBV), Q fever or Ross River virus (RRV) infections.

Methods: 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)-1b and IL-6] in sera and supernatants of peripheral blood mononuclear cell (PBMC) cultures was undertaken by specific ELISAs.

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

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

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