Chloroquine enhances the number of IL-10 producing cells and the expression of B7-2 and ICAM-1 in in vitro-cultured PBMC

Abstract

Chloroquine is prescribed as both an anti-malarial and an anti-inflammatory drug. However, its immuno-modulating effects remain largely unclear. Previous studies have shown that chloroquine inhibits antigen-induced proliferation, implying immuno-suppressive effects. In this study, we examined whether the inhibition of the proliferation reflects changes in the surface molecules that are important for T-cell activation and whether chloroquine affects the balance between pro- and anti-inflammatory cytokines. Chloroquine elevated the expression of the costimulatory and adhesion molecules B7-2 (CD86) and ICAM-1 (CD54) in peripheral mononuclear cells (PBMC). An increased percentage of CD14+ cells was also observed, and within this cell population, an increase in ICAM-1 expression was revealed by double-staining experiments. Assessment of the frequencies of interleukin (IL)-10 and interferon (IFN)-γ-producing cells in in vitro-cultivated PBMCs showed that the ratio between pro- and anti-inflammatory cytokines changed after exposure to chloroquine, favouring anti-inflammatory immune responses. This effect was mainly because of increased frequencies of IL-10-producing cells and was seen with or without the presence of stimulating antigens or mitogens. Our findings indicate that chloroquine affects the direction of the lymphocyte stimulation towards an anti-inflammatory response by affecting the antigen-presenting cells (APC) and the balance between pro- and anti-inflammatory cytokines, rather than generally inhibiting cytokine production.