The aim of this study was the evaluation of the release of bone-resorbing c
ytokines in peripheral blood mononuclear cells (PBMC) of patients with asep
tic loosening of Co-Cr hip prostheses. TNF-alpha, IL-6, and GM-CSF were mea
sured in both unstimulated and PHA-stimulated PBMC, and in PBMC cultured in
the presence of chromium and cobalt extracts. Blood samples from healthy d
onors were used as controls. Serum samples of both patients and healthy don
ors were tested to determine the concentration of metal ions. The proportio
n of lymphocyte, monocyte and lympocyte subpopulation in cultured PBMC did
not differ in patients and the control group. In unstimulated PBMC the rele
ase of TNF was significantly higher in patients than in the control group,
while IL-6 was significantly decreased and no change was observed for GM-CS
F. When the PBMC were challenged with chromium extract, all the 'index of c
ytokine release' resulted higher in patients than in the control group; cob
alt extract increased both the TNF and GM-CSF index, but not the index of I
L-6 release. Metal concentrations in serum from patients were significantly
increased and correlated with the TNF release in PBMC stimulated with both
metal extract. Our results suggest that a CoCr-implant releases a large am
ount of metal ions which could mediate the priming or the renewal of a cell
-mediated hypersensitivity reaction. The prevalence of circulating lymphocy
tes responsible for the delayed hypersensitivity, namely Th1, would justify
both the significant increase of TNF and the significant decrease of IL6 i
n unstimulated PBMC of patients, as well as the significant increase of the
'index of cytokine release' after the challenge with metal ions. (C) 1999
Elsevier Science Ltd. All rights reserved.