The central nervous system can regulate the peripheral immune system. Moreover, differences between left and right hemispheres (neurochemical brain asymmetries) and behavioral lateralization (functional brain asymmetries) affect immune responses. The molecular basis of brain-immune interactions remains insufficiently understood. Cytokines regulate immune responses, possibly through activation of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis activities are related to behavioral lateralization and brain asymmetry. Given IL-6 plays a role in asymmetrical brain immunomodulation, one might expect the IL-6 distribution in brain to be asymmetrical and to depend on behavioral lateralization. In order to start to test this hypothesis, male C57BL/6J mice were selected for paw preference and assessed for IL-6 levels in right and left cortex and hippocampus by enzyme linked immunosorbent assay. The results showed asymmetrical distribution of brain IL-6 in left-pawed animals and ambidextrous animals, but not in right-pawed animals, both in cortex and hippocampus. Furthermore, we found a correlation between IL-6 hemispheric distribution and the degree of behavioral lateralization both in cortex and hippocampus. Altogether, these results suggest that brain IL-6 could be a mediator of asymmetrical immunomodulation by the central nervous system.Copyright (c) 2005 S. Karger AG, Basel.