Biology Reference
In-Depth Information
12.2.6 Cytokines and Other Behaviors
Individual differences in the effects of cytokines or endotoxin on behavior have been
reported. LPS and IL-1 inhibit sexual behavior in female but not male rats, an effect
independent of cytokine influence on ovarian hormones
[41-43]
. Highly aggressive
ICR mice increase their startle response to mild social investigation after LPS treat-
ment, whereas mice from the low-aggression line show a decrease in startle amplitude
[44]
. IL-6-deficient mice are more aggressive in an inter-male aggression paradigm and
also show absence of stress-induced analgesia, implying changes in the opioid system
[45]
. IL-6 knockout mice also have an increased susceptibility to the convulsant effects
of N-methyl-D-aspartic acid (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid (AMPA), and kainate, suggesting that the excitatory amino acid system
is more active in these animals compared with normal controls. This also raises the
possibility that IL-6 knockout mice may be useful as a model for epilepsy.
The effects of peripherally administered IL-1 on sickness behavior are believed to
be NF- dependent, as central administration of NF- inhibitor peptide blocks the
sleep-inducing and pyrogenic effects of IL-1. However, following central administra-
tion, IL-1 activation of mitogen-activated protein kinase (MAP kinase) pathways
seems to be involved in the neural effects of this cytokine.
12.3 Specific Disorders in Which Cytokines May Produce
Behavioral Effects
The following subsections describe data relating to the behavioral effects of cyto-
kines evoked either following an external immunological challenge, or in the presence
of an inherent disorder of the immune system, as in autoimmune disease.
12.3.1 Acute Viral Infections
Upper respiratory tract infection, influenza, gastroenteritis, Epstein-Barr virus, and
cytomegalovirus are associated with behavioral symptoms that include anorexia,
lethargy, somnolence, irritability, poor concentration, reduced motor activity, and
depressed mood. The impairment of cognitive function associated with influenza has
been studied
[46]
, and a similar effect has been noted following infusion of IFN-
in healthy individuals
[47]
. Cognitive impairment was also noted in subjects with
laboratory evidence of influenza infection but an absence of other clinical symptoms.
The time course of the neuropsychiatric symptoms noted subsequently in acute viral
illness parallels that of physiological changes such as fever and somnolence.
12.3.2 Recurrent and Chronic Viral Infections
Herpes zoster and chronic hepatitis B are examples of recurrent and chronic viral
infections that are also associated with neuropsychiatric symptoms. Patients with
recurrent herpes zoster infections commonly report the onset of symptoms such as
