EFFECT OF AGING ON MURINE MACROPHAGES - DIMINISHED RESPONSE TO IFN-GAMMA FOR ENHANCED OXIDATIVE-METABOLISM

The ability of macrophages to secrete reactive oxygen intermediates, a s well as reactive nitrogen intermediates, correlates closely with the ir capacity to perform two critical effector functions: intracellular killing of microorganisms and lysis of tumor cells. In this study, age -associated changes in the ability of caseinate-elicited peritoneal ma crophages to release hydrogen peroxide were determined. Macrophages fr om aged BALB/c mice produced 50% less hydrogen peroxide than those fro m young mice in response to PMA or opsonized zymosan. In contrast, the production of macrophage-activating cytokines including IFN-gamma was not diminished in splenocyte supernatants from the aged group. Furthe rmore, no difference was detected in surface expression of IFN-gamma r eceptor in old and young mice. Macrophage responses to IFN-gamma, howe ver, declined with aging. In vitro, IFN-gamma-induced release of hydro gen peroxide and nitric oxide was 50% lower in old mice than in young mice. IFN-gamma-induced tyrosine phosphorylation of MAPK, an early act ivation event, was undetectable in macrophages from the aged mice. The se data demonstrate that diminished responses of macrophages to activa ting signals are one aspect of the impaired immune response in aged mi ce.