Effects of chromium extract on cytokine release by mononuclear cells.
We have evaluated the effects of chromium extract on the release by peripheral blood mononuclear cells (PBMCs) of cytokines favouring bone resorption. Furthermore, we have evaluated whether the chromium effects could be correlated with the activation and proliferation of PBMCs. Cell cultures were maintained in serum-free medium (AIM-V), in order to avoid the interference of exogenous growth factors. Increasing concentrations of chromium extract, ranging between 3 and 100%, were added to culture medium. Cytokine release (IL-1beta, TNFalpha, IL-6, GM-CSF and IFNgamma) was assessed on both PBMCs cultured with AIM-V only (unstimulated PBMC) and PBMCs cultured with AIM-V plus phytohaemagglutinina (PHA-stimulated PBMC). The activation and proliferation of PBMCs were evaluated by assessing DNA synthesis and soluble IL-2 receptor release, in order to determine whether an IL-2-dependent immune response can be induced by chromium. Our results show that in unstimulated PBMCs chromium ions slightly increased the release of pro-inflammatory cytokines, such as TNFalpha and IL-6, even though the increase is not significant. On the contrary, the different concentrations of chromium extract significantly inhibited the response to PHA stimulation, as shown by the decrease in IL-6 and sIL-2r release, and by the influence on cell viability and DNA synthesis. Both these effects are undesirable and support hypotheses on the biological effects of chromium. The continuous release of chromium from the implant could induce in PBMCs the release of bone-resorbing cytokines, which in the long term could be responsible for irreversible tissue damage. Moreover, chromium seems to inhibit the IL-2-dependent response of PBMCs, so that they are not able to trigger an efficient cell-mediated immune response.
Laboratory for Biocompatibility Research on Implant Materials, Istituti Ortopedici Rizzoli, Bologna, Italy. ior.biocomp@pt.tizeta.it
D
D
Granchi
E
E
Verri
G
G
Ciapetti
L
L
Savarino
E
E
Cenni
A
A
Gori
A
A
Pizzoferrato
D001862:Bone Resorption; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D004247:DNA / Q000097:blood; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000097:blood; D013268:Stimulation, Chemical
D016207:Cytokines; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D002857:Chromium; D004247:DNA