Chloroquine enhances the number of IL-10 producing cells and the expression of B7-2 and ICAM-1 in in vitro-cultured PBMC.
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)-gamma-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.
Hugosson
E
E
The Department of Immunology, Stockholm University, Stockholm, Sweden. ehugosson@hotmail.com
Björkman
A
A
Troye-Blomberg
M
M
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis*; D000962:Antimalarials / Q000494:pharmacology*; D051940:B7-2 Antigen; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis*
D015703:Antigens, CD; D000962:Antimalarials; D051940:B7-2 Antigen; C497964:CD86 protein, human; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D007371:Interferon-gamma; D002738:Chloroquine