Aging alters the production of iNOS, arginase and cytokines in murine macrophages

The limited amount of information on the primary age-related deficiencies in the innate immune system led us to study the production of inducible nitric oxide synthase (iNOS), arginase, and cytokines in macrophages of young (8 weeks old) and old (72 weeks old) female BALB/c mice. We first evaluated iNOS and arginase inducers on peritoneal (PM phi) and bone marrow-derived (BMM phi) macrophages of young BALB/c and C57BL/6 mice, and then investigated their effects on macrophages of old mice. Upon stimulation with lipopolysaccharide (LPS), resident and thioglycolate-elicited PM phi from young mice presented higher iNOS activity than those from old mice (54.4%). However, LPS-stimulated BMM phi from old mice showed the highest NO levels (50.1%). Identical NO levels were produced by PM phi and BMM phi of both young and old mice stimulated with interferon-gamma. Arginase activity was higher in resident and elicited PM phi of young mice stimulated with LPS (48.8 and 32.7%, respectively) and in resident PM phi stimulated with interleukin (IL)-4 (64%). BMM phi of old mice, however, showed higher arginase activity after treatment with IL-4 (46.5%). In response to LPS, PM phi from old mice showed the highest levels of IL-1 alpha (772.3 +/- 51.9 pg/mL), whereas those from young mice produced the highest amounts of tumor necrosis factor (TNF)-alpha (937.2 +/- 132.1 pg/mL). Only TNF-alpha was expressed in LPS-treated BMM phi, and cells from old mice showed the highest levels of this cytokine (994.1 +/- 49.42 pg/mL). Overall, these results suggest that macrophages from young and old mice respond differently to inflammatory stimuli, depending on the source and maturity of the cell donors.