CYTOKINE-SPECIFIC CENTRAL MONOAMINE ALTERATIONS INDUCED BP INTERLEUKIN-1, INTERLEUKIN-2 AND INTERLEUKIN-6

Cytokine-specific alterations of monoamine activity were evident in th e hypothalamus, hippocampus and prefrontal cortex 2 h following periph eral administration of recombinant interleukin (IL)-1 beta, IL-2 and I L-6 (200 ng, i.p.) in male, BALB/c mice. IL-1 induced the broadest ran ge of neurochemical changes, affecting central norepinephrine (NE), se rotonin (5-HT) and dopamine (DA) activity. In particular, IL-1 enhance d NE turnover in the hypothalamus and hippocampus, 5-HT turnover in th e hippocampus and prefrontal cortex (owing to increased utilization an d reduced content of the transmitters in these brain regions), and enh anced DA utilization in the prefrontal cortex. IL-6 increased 5-HT and DA activity in the hippocampus and prefrontal cortex in a manner simi lar to IL-1, but failed to affect central NE activity. Moreover, IL-2 increased hypothalamic NE turnover (reflecting a profound increase in NE utilization) and enhanced DA turnover in the prefrontal cortex, but did not influence central 5-HT activity. Hence, these cytokines diffe rentially altered neurochemical activity in brain regions that mediate neuroimmune interactions and that are influenced by physical and psyc hological stressors. In addition to the neurochemical changes, plasma corticosterone concentrations were profoundly enhanced in IL-l-treated animals, but not significantly altered by IL-2 or IL-6 treatment. The IL-l-induced corticosterone elevations did not significantly correlat e with alterations of hupothalamic NE activity.