The inflammatory response to social defeat is increased in older mice

Previous research indicates that repeated social defeat of mice causes increased lymphocyte trafficking to the spleen, elevated proinflammatory cytokine production, and induced glucocorticoid insensitivity in splenocytes. Social defeat also causes increases in anxiety-like behavior. This study investigated whether repeated social defeat results in similar immunoregulatory and behavioral changes in older mice as those seen previously in young adult mice. The data revealed that, regardless of age, defeated mice had significantly more splenic CD11b+ Gr-1+ monocytes and neutrophils than controls. Supernatants harvested from cultured splenocytes from older mice contained comparatively higher IL-6 and TNF-alpha than supernatants from younger animals. In addition, those same cells derived from older defeated mice were hypersensitive to lipopolysaccharide (LPS) and insensitive to glucocorticoids in vitro. As seen previously in young adult mice, social defeat caused an increase in anxiety-like behavior in the open field test, but had no effect on learned helplessness in the forced swim test. These data indicated that repeated social defeat results in a proinflammatory state that is exacerbated in older mice. The implications of these data are noteworthy, given the strong role of inflammation in many age-related diseases. (C) 2007 Elsevier Inc. All rights reserved.