Total serum IL-12 and IL-12p40, but not IL-12p70, are increased in the serum of older subjects; relationship to CD3(+)and NK subsets.
Interleukin 12 (IL-12), a central cytokine acting on T and natural killer (NK) cells, directs proliferation of activated T lymphocytes towards a Th1 phenotype. The heterodimeric molecule IL-12p70, equates with IL-12 biological activity, while IL-12p40 may antagonize IL-12 and inhibit cytotoxic T lymphocyte (CTL) generation in vitro. This study characterizes age-related changes in serum total IL-12, IL-12p70 and IL-12p40 relating them with CD3(+), NK and related subsets from subjects, aged 30-96 years. Total IL-12, IL-12p40 and the IL-12p40/IL-12p70 ratio, but not IL-12p70, increased significantly with age (P<0.0001). Increases in total IL-12 and IL-12p40 were negatively associated with CD3(+)(P=0.003, P=0.002), CD3(+)CD4(+)(P=0.004, P=0.003), CD3(+)CD8(+)(P=0.04;P=0. 04) and CD4(+)45RA(+)(P=0.0003;P=0.0007) subsets, respectively. Conversely, increases in IL-12p40 showed a non-significant trend for association with increases in NK(P=0.07) and a related CD8(+low)CD57(+)(P=0.07) subset. These findings may have important implications for understanding the functional activity of IL-12 and its p40 and p70 subunits in vivo and with respect to T-or NK-cell activation in aging.