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 p henotype, The heterodimeric molecule IL-12p70, equates with IL-12 biologica l activity, while IL-12p40 may antagonize IL-12 and inhibit cytotoxic T lym phocyte (CTL) generation in vitro, This study characterizes age-related cha nges 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-12 p40 and the IL-12p40/IL-12p70 ratio, but not IL-12p70, increased significan tly with age (P<0.0001). Increases in total IL-12 and IL-12p40 were negativ ely 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 h ave 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 ac tivation in aging. (C) 2000 Academic Press.