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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Last Modified November 25, 2009