Interleukin-2 and -6 induce behavioral-activating effects in mice

Interleukin (IL)-1, IL-2 and IL-6 influence central monoamine activity in a cytokine-specific manner. We demonstrated that whereas IL-2 increased hypothalamic and hippocampal norepinephrine (NE) utilization, and DA turnover in the prefrontal cortex, IL-6 induced profound elevations of serotonin (5-HT) and mesocortical dopamine (DA) activity in the hippocampus and prefrontal cortex [S. Zalcman, J.M. Green-Johnson, L. Murray, D.M. Nance, D.G. Dyck, H. Anisman, A. H. Greenberg, Cytokine-specific central monoamine alterations following IL-1, -2 and -6 administration, Brain Res. 643 (1994) 40-49]. IL-1, in contrast, induced a wide range of central monoamine alterations. We presently report that these cytokines also differentially influence behavior. Profound reductions in non-ambulatory and ambulatory exploration were induced in BALB/c mice following IL-1 administration. In contrast, IL-2-treated mice displayed significant increases in the time spent engaged in non-ambulatory exploration, digging, rearing (particularly the number of free rears), and in the investigation of a novel stimulus (i.e., increased number and duration of stimulus contacts). IL-6-treated mice, moreover, exhibited significant increases in the time spent engaged in ambulatory exploration, digging and rearing (particularly the number of free rears, which tended to be of short duration). Modest increases in locomotion and grooming were also observed in IL-6-treated animals. Plasma corticosterone levels did not vary significantly as a function of IL-6 treatment. Hence, cytokine-specific behavioral-activating effects were induced following administration of IL-2 and IL-6. We suggest that these effects have adaptive significance and relevance to sickness behavior; however, pathological outcomes (e.g., schizophrenia, anxious-like states, anxious depression, motor abnormalities) could develop should these cytokines be overproduced or dysregulated.