Several lines of evidence point to a profound remodelling of the cytokine n
etwork in healthy elderly subjects, with decreased type-1 cytokine producti
on (IL 2) and a shift to type 0 and 2. We have also observed an increase of
proinflammatory cytokines (IL-1, IL-6, TNF-alpha) in vitro, and an increas
e of circulating stem cell factor in vivo. In this setting, we studied chan
ges of chemokines (MCP-I and RANTES) with aging, as well as other molecules
, namely, sTNF-RI and sTNF-RII, and the soluble form of the CD30 molecule (
sCD30), involved in the pro- and antiinflammatory cytokine balance. The sub
jects enrolled in the study belonged to three different selected healthy gr
oups of young, aged and centenarians. The presence of rheumatoid factor (RF
) and antinuclear antibodies (ANA) was simultaneously assessed. The results
show that MCP-1 serum levels were higher in the healthy aged and lowest in
the young, while RANTES increased exclusively in centenarians. Only centen
arians had autoantibodies (ANA and RF). sTNF-RI and sTNF-RII were significa
ntly elevated in healthy old subjects compared to the young, and even highe
r in selected centenarians compared to the other age groups, sCD30 serum le
vels were significantly raised in centenarians compared to the young, despi
te absence of circulating CD30 + cells in the peripheral blood of the whole
study population. No relationship among serum values of these different me
mbers of the TNF-R family was found, despite a strong correlation for sTNF-
RI and sTNF-RII in all groups. We hypothesize that the increased chemokine
levels in aged people, and raised sCD30 levels in centenarians, may reflect
a general shift towards type 0/2 cytokines in normal aging, which may be r
esponsible, at least in part, for the appearance of circulating autoantibod
ies without definite clinical consequences at advanced age. (C) 2000 Elsevi
er Science Ireland Ltd. All rights reserved.