Cytokines and Stress in Relation
to Neurochemical Change & Behavior
Communication may occur between the immune and
central nervous system, and cytokines (signaling molecules of the immune
system) may act as messengers (immunotransmitters) in this respect. The
immune system may act like a sensory organ informing the brain of antigenic
challenge, and given the nature of the neurochemical changes elicited
by cytokines, immune activation may be interpreted by the CNS as a stressor.
It has been our contention that the immune system may be part of a regulatory
loop that, by virtue of its effects on CNS functioning, might contribute
to the symptoms of behavioral pathologies, including mood and anxiety-related
disorders, and may contribute to cognitive disturbances frequently seen
during immunotherapy in cancer patients.
Several macrophage-derived cytokines, such as interleukin
(IL)-1b, IL-6, and tumor necrosis factor-a (TNF-a), as well as IL-2 secreted
from T-helper cells, may be particularly important in subserving immune-brain
communication. The objective of this aspect of our research program is
to elucidate the potential neurochemical and behavioral sequelae of immune
and cytokine challenge. Our ongoing research, assesses the effects of
systemic and central cytokine administration (e.g., IL-1b, IL-6, TNF-a)
on central monoamine and neuropeptide activity in brain regions where
stressors ordinarily have profound effects. As well, we assess whether
synergistic behavioral, neuroendocrine and neurotransmitter effects occur
between cytokines and stressors, and whether cytokine activation induces
a sensitization effect so that subsequent responses to either cytokine
treatment or stressor challenges are enhanced.
If cytokines play a role in affective illness,
then it would be expected that cytokine challenge (like stressors) will
induce behavioral changes reminiscent of depressive symptomatology (e.g.,
anhedonia) and will provoke anxiogenic effects. Thus, the neurochemical
effects of stressors are paralleled by studies to assess the behavioral
effects of cytokine treatments. These include several tests of anhedonia,
exploratory profiles, sickness behaviors, working and reference memory
changes, as well as several different tests of anxiety.
Supported by CIHR.
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