Named Series: Twenty Years of Brain Behavior and ImmunityTwenty years of research on cytokine-induced sickness behavior
Introduction
The first paper on sickness behavior was published in Brain, Behavior, and Immunity (BBI) by Aubert et al. (1995). Since then, 39 papers on sickness behavior have been published in the journal, which represent 20 percent of the 192 papers published on cytokine-induced sickness behavior that are listed in PubMed. Despite some risk of overlap, it would be fair to add to these statistics the 14 papers on cytokines and depression that were published in BBI in 2002. Although the familiar phrase that “statistics lie and statistician’s use statistics” is apropos in the sense that statistics can be used to describe nearly anything one wants them to tell, it is clear from this cursory quantitative review of the literature that BBI has been instrumental in promoting the concept of cytokine-induced sickness behavior. This conclusion becomes even more obvious when these figures are compared to the 52 papers on cytokines and the brain that were published by BBI and contrast with the 15,382 papers listed by PubMed in this field (as of July 27, 2006). BBI has not been the home journal of those scientists who study the expression and actions of cytokines in the brain. Its niche is clearly at the interface between immunity and behavior in physiological and pathological conditions. The objective of this article is not to add another paper on cytokine-induced sickness behavior to the list of those already published by BBI but to show why it was and remains logical for BBI to play an instrumental role in the publication of the results on cytokine-induced sickness behavior.
Section snippets
Before 1987: The history of sickness behavior
The study of sickness has a rich history in psychology and behavioral pharmacology (Fig. 1). In psychology, research on the concept of sickness started in the mid-fifties with Garcia’s work on bait shyness (Garcia et al., 1955). Garcia explained the fact that rodents cannot be poisoned very easily by their propensity to develop learned aversions to the new taste of any compound that induces gastro-intestinal malaise. At the time this research was carried out, the laws of learning were dominated
From 1987 to 1996: The merging of sickness behavior with immunology
The way the concept of sickness behavior merged with immunology is summarized in Fig. 2. Prior to 1987, the biological activities of “endogenous pyrogen,” “leukocyte endogenous mediator,” and “lymphocyte activating factor” were suspected to be derived from a single protein. That protein was eventually purified, renamed as IL-1, and was shown to be active in the brain, as determined by induction of both fever in rabbits and EEG signals associated with slow-wave sleep in rats. However, the very
From 1997 to 2006: The move from sickness to depression
The way the concept of cytokine-induced sickness behavior merged with the field of mental health is illustrated in Fig. 3. Defining cytokine-induced sickness behavior as a motivational state implies that it belongs in the realm of physiology, just as fear, hunger, thirst and other motivational states. To be able to withdraw from the environment, seek rest and care for the body is as normal in response to infectious agents as being able to shift to a state of increased arousal and readiness for
2007 and beyond: The move to translational research
Cytokine-induced sickness behavior is no longer a curiosity. In animal research, its measurement has become a standard procedure for assessing the mode of functioning of communication pathways from the immune system to the brain as well as the sensitivity of the brain to direct immune stimulation. At the clinical level, many investigators are now actively engaged in collecting the type of evidence that is necessary to test the possibility that many of the subjective complaints of patients
Acknowledgment
This work was supported by the NIH to K.W.K. (MH51569 and AI50442) and R.D. (MH71349).
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