Suppression of interleukin-2 and interleukin-2 receptor biosynthesis by gold compounds in in vitro activated human peripheral blood mononuclear cells.
OBJECTIVE
To further investigate the mechanism of action of gold compounds by studying their effects on interleukin-2 (IL-2) and IL-2 receptor (IL-2R) biosynthesis.


METHODS
We cultured phytohemagglutinin- or anti-CD3 antibody-activated normal peripheral blood mononuclear cells (PBMC), as well as the erythroleukemic K562 cell line, in the presence of gold sodium thiomalate or auranofin. Tritiated thymidine incorporation assays, cytotoxicity assays, immunofluorescence analysis, enzyme-linked immunosorbent assay, Northern blot, and RNA dot-blot hybridization were used.


RESULTS
Gold compounds, at concentrations attainable in vivo, inhibited the proliferation of normal PBMC, with no evidence of direct cytotoxicity. This inhibitory effect was associated with a dose-dependent suppression of both IL-2 and IL-2R messenger RNA accumulation. In contrast, the same concentrations of gold compounds failed to inhibit the spontaneous proliferation of the IL-2-independent K562 cells.


CONCLUSIONS
Our findings suggest an IL-2/IL-2R-mediated mechanism for suppression of lymphocyte proliferation by gold compounds, which might account for the immunomodulatory effects of gold in patients with rheumatoid arthritis.
Sfikakis
P P
PP
First Department of Internal Medicine, Athens University Medical School, Laikon Hospital, Greece.
Souliotis
V L
VL
Panayiotidis
P P
PP
D000906:Antibodies / Q000494:pharmacology; D001310:Auranofin / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics
D000906:Antibodies; D017252:CD3 Complex; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D006052:Gold Sodium Thiomalate; D001310:Auranofin