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 imp ortant in the pathogenesis of RA, but it is not known whether Chi acts via inhibition of T cell function. We here present evidence that Chi, just like cyclosporine A (CsA), inhibits T cell proliferation as indu ced with immobilized alpha CD3 MoAb in a concentration-dependent manne r, at least partly through interfering with the production of IL-2 pro tein and the induction of IL-2 mRNA. Furthermore, Chi impedes the resp onsiveness of T cell clones to IL-2 since (1) the inhibition of alpha CD3 MoAb-induced proliferation by Chi could not be reversed by rIL-2 a nd (2) Chi directly blocks IL-2-driven proliferation of cloned T cells . Chi appeared to interfere with the internalization (50% inhibition) and degradation (total blockade) of rIL-2. Finally, the combination of Chi and CsA synergistically inhibited T cell proliferation. We conclu de that Chi may inhibit functional properties of human T cells, althou gh 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.