Chloroquine inhibits T cell proliferation by interfering with IL-2 production and responsiveness.
Chloroquine (Chl) is an anti-rheumatic drug that is widely used in the treatment of rheumatoid arthritis (RA). It seems that T cells are important in the pathogenesis of RA, but it is not known whether Chl acts via inhibition of T cell function. We here present evidence that Chl, just like cyclosporine A (CsA), inhibits T cell proliferation as induced with immobilized alpha CD3 MoAb in a concentration-dependent manner, at least partly through interfering with the production of IL-2 protein and the induction of IL-2 mRNA. Furthermore, Chl impedes the responsiveness of T cell clones to IL-2 since (1) the inhibition of alpha CD3 MoAb-induced proliferation by Chl could not be reversed by rIL-2 and (2) Chl directly blocks IL-2-driven proliferation of cloned T cells. Chl appeared to interfere with the internalization (50% inhibition) and degradation (total blockade) of rIL-2. Finally, the combination of Chl and CsA synergistically inhibited T cell proliferation. We conclude that Chl may inhibit functional properties of human T cells, although the drug is 100- to 1000-fold less potent than CsA in inhibiting T cell proliferation and IL-2 production, respectively. It is speculated that the in vitro effects of Chl might be relevant in explaining the anti-rheumatic effect of this drug in patients with RA.
Landewé
R B
RB
Department of Rheumatology, University Hospital, Leiden, The Netherlands.
Miltenburg
A M
AM
Verdonk
M J
MJ
Verweij
C L
CL
Breedveld
F C
FC
Daha
M R
MR
Dijkmans
B A
BA
D000911:Antibodies, Monoclonal / Q000276:immunology; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D002738:Chloroquine / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016572:Cyclosporine; D002738:Chloroquine