Effect of cyclosporin on apoptosis in human cultured monocytic THP-1 cells and synovial macrophages.
OBJECTIVE
Cyclosporin A (CyA) is an immunosuppressant drug used for the treatment of rheumatoid arthritis (RA), that might affect programmed cell death (apoptosis) of the cells involved in the synovial inflammatory reaction. The effects of CyA on apoptosis were evaluated on cultured human monocytic myeloid cells (THP-1 cell line) and on RA synovial macrophages.


METHODS
In order to induce THP-1 cell differentiation into adherent cells, an amount of these was treated with human recombinant IFN-gamma before incubation with CyA. Primary cultures of synovial macrophages were obtained from RA patients and treated in vitro with CyA.


RESULTS
CyA, at the pharmacological range (100-300 ng/ml) employed in the treatment of RA, seems to induce, after 48-96 hrs, programmed cell death in differentiating THP-1 cells, whereas cultured synovial macrophages (fully differentiated monocytic cells) do not show any apoptosis at the same time.


CONCLUSIONS
Short-term CyA treatment may induce increased apoptosis in immature and differentiating cultured monocytes. Cultured synovial macrophages (resident monocytic-derived and differentiated cells) seem to be resistant to the treatment as far as apoptosis is concerned.
Cutolo
M
M
Division of Rheumatology, University of Genova, Italy.
Barone
A
A
Accardo
S
S
Setti
M
M
Villaggio
B
B
D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000494:pharmacology; D007719:Knee Joint / Q000473:pathology / Q000601:surgery; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology*; D011994:Recombinant Proteins; D013583:Synovial Membrane / Q000166:cytology*
D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016572:Cyclosporine; D004247:DNA