Central monoamine activity following acute and repeated systemic interleukin-2 administration

Interleukin-2 (IL-2), together with other cytokines, may be involved in communication between the immune system and the CNS. Moreover, IL-2 alterations have been implicated in psychiatric disorders, and IL-2 immunotherapy may engender neuropsychiatric and cognitive disturbances. Given the presumed relationship between mood disturbances and monoamine activity, the present investigation was undertaken to determine the central monoamine alterations associated with acute and repeated systemic IL-2 administration in mice. Acute, systemic IL-2 (0.55-17.6 x 10(3) IU) did not influence plasma adrenocorticotropic hormone or corticosterone levels, but increased the utilization of norepinephrine (NE) within the paraventricular nucleus of the hypothalamus. In contrast to the effects of acute IL-2 administration, when administered repeatedly (for 7 days), IL-2 increased NE utilization within the median eminence plus arcuate nucleus and in the hippocampus, and to a lesser extent in the central amygdala and medial prefrontal cortex. These changes in utilization were accompanied by increased levels of NE within the median eminence plus arcuate nucleus and central amygdala, and reduced NE within the locus coeruleus. As well, serotonin (5-hydroxytryptamine; 5-HT) levels were altered within the hippocampus and prefrontal cortex, and dopamine turnover was reduced within the caudate and substantia nigra. The finding of altered central neurotransmitter activity needs to be considered in the context of the marked cognitive/memory impairments, as well as the neuropsychiatric symptoms, which are associated with IL-2 immunotherapy in humans.