Interferon-gamma-induced priming for secretion of superoxide anion and tumor necrosis factor-alpha declines in macrophages from aged rats.

Macrophage responses to recombinant IFN-gamma decline during aging, as measured by two criteria of macrophage activation, O2- and TNF-alpha secretion. The production of O2- by macrophages in response to opsonized-zymosan and recombinant rat IFN-gamma is 75% lower in 23-month-old rats than in 3-month-old rats. Furthermore, the secretion of TNF-alpha in response to IFN-gamma and LPS is almost absent in macrophages from aged rats. Production of both O2- and TNF-alpha by resident peritoneal macrophages from specific pathogen-free aged rats in response to priming and triggering stimuli was partially or fully restored by implantation of syngeneic pituitary grafts from young rats. These data demonstrate that macrophages from aged rats are defective in their response to a priming signal induced by IFN-gamma, and they suggest that impaired macrophage responses during aging may be reversible.