Age Effects on Macrophage Function Vary by Tissue Site, Nature of Stimulant, and Exercise Behavior

We explored the effects of aging on macrophage function in male BALB/c mice from three age groups: young (2 months), middle-aged (12 months), and old (21 months). Macrophages were collected from alveoli, peritonea, and spleens of each age group. Cells were cultured in vitro with LPS or LPS+IFN-gamma and assayed for production of IL-1, IL-12, NO, and TNF-alpha. Using herpes simplex virus-1, age-related changes in intrinsic antiviral resistance (plaque assay) and extrinsic antiviral resistance (NO and TNF-alpha production) were determined in alveolar and/or peritoneal macrophages. Effects of chronic exercise on age-related macrophage changes were examined. In vitro, macrophages from the alveoli and spleen of older mice generally produced more cytokine and NO compared to younger counterparts. Conversely, macrophages from the peritonea of older mice generally produced less cytokine and NO in vitro compared to younger counterparts. Alveolar macrophages from both old and young mice showed higher intrinsic antiviral resistance to HSV-1 compared to middle-aged mice, while peritoneal macrophages from young mice showed reduced intrinsic resistance compared to those from both middle-aged and old mice. When challenged with HSV-1, a trend towards decreased peritoneal macrophage production of TNF-alpha and decreased alveolar macrophage production of IL-12 with advancing age was found. Chronic moderate exercise tended to reverse age-associated changes in macrophage function in old mice.