Cyclosporine and chloroquine synergistically inhibit the interferon-gamma production by CD4 positive and CD8 positive synovial T cell clones derived from a patient with rheumatoid arthritis.
OBJECTIVE
To investigate synergistic interaction between cyclosporine (Cy) and chloroquine (Chl) in an in vitro system, with regard to interferon-gamma (IFN) production by OKT3 activated T cell clones.


METHODS
CD4+ and CD8+ T cell clones, derived from synovial tissue of a patient with rheumatoid arthritis (RA) were activated with plastic coated OKT3 monoclonal antibody in the presence or absence of various concentrations of Cy, Chl and their combinations. After 24 h of incubation the supernatants were assayed for IFN by ELISA:


RESULTS
Cy as well as Chl were able to completely inhibit in a concentration dependent fashion the IFN production by CD4+ and CD8+ T cell clones. Combinations of Cy and Chl, which in themselves give minor inhibition of IFN production, were able to inhibit in a synergistically enhanced fashion the production of IFN by these clones. The synergy was formally proven by the construction of isoboles. This synergy was most pronounced when drug concentrations were used which individually gave minor inhibition of IFN production.


CONCLUSIONS
We conclude that the results of our in vitro experiments may give rise to further investigation of the promising combination of Cy and Chl in the treatment of RA.
Landewé
R B
RB
Department of Rheumatology, University Hospital, Leiden, The Netherlands.
Miltenburg
A M
AM
Breedveld
F C
FC
Daha
M R
MR
Dijkmans
B A
BA
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D013583:Synovial Membrane / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015704:CD4 Antigens; D016827:CD8 Antigens; D007371:Interferon-gamma; D016572:Cyclosporine; D002738:Chloroquine