Nfl. Spencer et al., DYSREGULATION OF IL-10 PRODUCTION WITH AGING - POSSIBLE LINKAGE TO THE AGE-ASSOCIATED DECLINE IN DHEA AND ITS SULFATED DERIVATIVE, Experimental gerontology, 31(3), 1996, pp. 393-408
Peripheral lymphoid cells isolated from the spleens and peritoneal cav
ities of aged mice were found to constitutively secrete the multifunct
ional cytokine interleukin (IL)-10 when cultured in vitro. B-Lymphocyt
es were implicated as the cell type responsible. Abnormal expression o
f this cytokine was also detected in vivo because high levels of mRNA
for IL-10 were present in splenocytes freshly isolated from aged anima
ls, In addition to the spontaneous secretion of IL-10, lymphoid cells
from aged donors were hyperresponsive to exogenous stimulation with en
dotoxin, producing exaggerated quantities of both IL-10 and IL-6 in cu
lture. Treatment of aged animals with dehydroepiandrosterone sulfate (
DHEAS), a natural steroid, reversed the age-associated alterations in
cytokine production, rendering the treated mice quite similar to matur
e adult controls. DHEAS treatment of aged mice also resulted in a lowe
ring in the number of B1 cells present in the peritoneal cavity and al
so reduced the titers of circulating autoantibodies specific for phosp
hatidylcholine (PtC), Based on its wide range of biologic activities,
a dysregulation in the mechanisms that control IL-10 production could
be a major contributor to immunosenescence. The ability of DHEAS treat
ment to restore normal control over the expression of IL-10 may explai
n how this steroid enhances immunocompetence in aged animals.